Loco – EMBRYOLOGY

• Intramembranous ossification is the process by which bone develops directly from mesenchymal tissue without first being modeled in cartilage.

• Examples: flat bones of the skull, mandible, clavicle.

• Mesenchymal cells → osteoblasts → secrete osteoid → mineralization → direct bone formation.

🔴 Why the others are wrong

• Endochondral → Bone forms after a cartilage model is laid down. Example: long bones (femur, tibia).

• Non-lamellar → Refers to immature/woven bone, not a developmental process.

• Intracartilaginous → Another name for endochondral ossification, which does involve cartilage first, so incorrect here.

• Lamellar → Mature organized bone structure, not the method of initial formation.

• Apoptosis (programmed cell death) is critical in embryological development.
• In limb development, apoptosis removes the interdigital tissue (the webbing between fingers and toes).
• If apoptosis fails → the tissue persists → syndactyly (fused/webbed digits).

Why the other options are incorrect

• All bones would form as the same structure
  ❌ Bone patterning depends on Hox genes and signaling pathways (not apoptosis).
• The proximo-distal patterning would not occur normally
  ❌ Controlled by apical ectodermal ridge (AER) and fibroblast growth factors (FGFs), not apoptosis.
• The bones and muscles would not form
  ❌ That would be due to failure of mesodermal differentiation, not apoptosis.
• The overlying epidermis would not form
  ❌ Epidermis derives from ectoderm, not related to apoptosis failure.

When considering the formation of bones and cartilage of the limbs (upper and lower), we’re referring to the appendicular skeleton, which has a different embryological origin compared to the axial skeleton (skull, vertebrae, ribs).

🔹 Lateral Plate Mesoderm — Limb Bones:

• The lateral plate mesoderm splits into:

  • Parietal (somatic) layer

  • Visceral (splanchnic) layer

• The parietal/somatic layer gives rise to:

  • Bones and connective tissue of the limbs

  • Sternum

  • Parts of the body wall

Limb development begins with limb bud formation, where mesenchyme derived from the lateral plate mesoderm condenses to form cartilage models, which then ossify to become bones.

❌ Why the Other Options Are Incorrect:

Paraxial mesoderm

• Forms somites, which contribute to:

  • Axial skeleton(vertebrae, ribs, base of skull)

  • Skeletal muscle and dermis

• Does not form limb bones, although limb muscles do come from here (myotome)

Intermediate mesoderm

• Develops into the urogenital system

• No contribution to limb skeleton

Endoderm

• Forms gut tube and internal linings — not involved in musculoskeletal development

Ectoderm

• Forms epidermis and nervous system

• Does not form bones or cartilage. However, it interacts with mesoderm to pattern limb development

• In second week of development (week of twos):

  • The blastocyst has trophoblast (cyto- + syncytiotrophoblast) outside and embryoblast (epiblast + hypoblast) inside.

  • Hypoblast forms the exocoelomic (Heuser’s) membrane, lining the blastocoel, creating the primary yolk sac.

  • Soon, a new layer — the extraembryonic mesoderm — develops between the exocoelomic membrane and the cytotrophoblast.

  • Cavities appear in this mesoderm → coalesce to form the extraembryonic coelom (chorionic cavity).

• This layer later differentiates into:

  • Somatopleuric extraembryonic mesoderm → lining cytotrophoblast.

  • Splanchnopleuric extraembryonic mesoderm → covering yolk sac.

Why not the others?

• Extraembryonic membrane and cytotrophoblast → vague, not specific. ❌

• Extraembryonic membrane and syncytiotrophoblast → incorrect, syncytiotrophoblast is outside cytotrophoblast. ❌

• Syncytiotrophoblast and cytotrophoblast → that’s where lacunae form, not extraembryonic mesoderm. ❌

• None of these → incorrect, because the correct relation is well-known. ❌

Implantation is the process by which the blastocyst attaches to and embeds into the uterine wall (specifically, the endometrium) to establish pregnancy. This crucial step occurs around 6-7 days after fertilization.

The key player responsible for actively facilitating implantation is the syncytiotrophoblast.

The syncytiotrophoblast is a multinucleated, invasive cell mass that arises from the outer layer of the trophoblast during the blastocyst stage. Once the blastocyst makes contact with the endometrial lining, the trophoblast differentiates into two layers:

• Cytotrophoblast: the inner cellular layer that serves as a stem cell population.
• Syncytiotrophoblast: the outer, multinucleated layer that invades the endometrium.

The syncytiotrophoblast plays the primary role in implantation by:

• Producing enzymes that digest and break down the endometrial tissue, allowing the blastocyst to embed.
• Secreting human chorionic gonadotropin (hCG), which maintains the corpus luteum and sustains progesterone production — crucial for maintaining the uterine lining.
• Extending finger-like projections that penetrate deep into the endometrium, securing the blastocyst.

Therefore, the correct answer is

syncytiotrophoblast

.

🔍 Why the Other Options Are Incorrect:

Ectoderm is one of the three germ layers that form later during gastrulation. It gives rise to the skin, nervous system, and related structures, but it plays no role in implantation.

Cytotrophoblast is the inner layer of the trophoblast that provides proliferative cells to the syncytiotrophoblast. While essential for growth and maintenance, it is not directly invasive and does not lead the implantation process.

Endometrium is the maternal uterine lining where implantation occurs. While it is the site of implantation, it is the target rather than the active player facilitating the process.

Uterine fluid nourishes the blastocyst before implantation but plays no active role in the implantation process itself.

• The apical ectodermal ridge (AER) is a distal ectodermal structure at the tip of the limb bud.

• It secretes fibroblast growth factors (FGFs) to maintain the progress zone in the underlying mesoderm.

• If the AER is removed, cells in the progress zone stop proliferating toward the distal end.

• Consequently, structures that have already started forming proximally develop, but new distal structures do not form, illustrating the AER’s role in proximodistal patterning.

❌ Why Other Options Are Incorrect:

• Regeneration of the entire limb bud from underlying mesoderm → Limb cannot fully regenerate without continuous AER signaling.

• Degeneration of the limb bud → Only distal growth stops; proximal structures still form.

• Regeneration of new apical ridge from adjacent epidermal tissue → Normally does not happen in limb development.

• Continued development in the progress zone, once the apical ridge has induced it → Distal formation requires ongoing AER signaling.

The clavicle is unique in its ossification because it shows both intramembranous and endochondral ossification, making this the incorrect statement.

✅ Correct facts about clavicle development:

• It is the first bone to begin ossification, starting around the 5th to 6th week of gestation.

• It has 2 primary ossification centers, one on each side of the shaft, which fuse early.

• It also has 1 secondary ossification center at the sternal end, which appears during adolescence and fuses around 21–25 years of age, making it the last bone to complete ossification.

❌ Why the selected option is incorrect:

• Saying it ossifies “solely via intramembranous ossification” is incorrect.

• Although most of the clavicle forms by intramembranous ossification, the sternal (medial) end undergoes endochondral ossification — a rare feature for a flat bone.

❌ Why the Other Options Are Correct

• It ossifies from 2 primary centers of ossification: ✅ True

• It is the 1st bone to begin ossification: ✅ True

• It is the last to finish ossification at around 21–25 years of age: ✅ True

• Ossification begins between the 5th and 6th weeks of gestation: ✅ True

🔹 Key Facts About Achondroplasia:

• Cause:

  • Mutation in the FGFR3 gene (Fibroblast Growth Factor Receptor 3)

  • This mutation causes constitutive activation of the receptor.

• Effect:

  • FGFR3 normally inhibits chondrocyte proliferation in the growth plate.

  • In achondroplasia, excessive inhibition occurs, leading to failure of endochondral ossification (longitudinal growth).

• Results in:

  • Short limbs (rhizomelic shortening — affects proximal segments like femur and humerus)

  • Normal trunk size

  • Macrocephaly with frontal bossing

• Most common cause of dwarfism, specifically disproportionate short stature

❌ Why “Failure of horizontal bone growth” Is Incorrect:

• Horizontal (appositional) bone growth refers to width expansion, which is regulated by intramembranous ossification, not endochondral ossification.

• Achondroplasia does not impair appositional growth, so bone width is generally normal.

• The limbs are short, but not narrow — giving the classic appearance of disproportionate dwarfism.

The skeletal system, particularly the limbs, has a well-orchestrated timeline and morphological process during embryonic development. This includes limb bud formation, apical ectodermal ridge (AER) activity, mesenchymal proliferation, chondrification, ossification, and joint formation.

Let’s explore each option:

✅ Option A: Fingers and toes formation occur due to death of apical ectodermal ridge cells by apoptosis

✔️ Correct

• Apical ectodermal ridge (AER) is a thickened ectodermal structure that plays a vital role in limb outgrowth and patterning.

• Apoptosis (programmed cell death) in the AER and surrounding tissues (especially in the interdigital zones) is responsible for separating digits (fingers and toes).

• Failure of this apoptosis results in syndactyly (webbed fingers or toes).

• This process occurs around weeks 6–8 of development.

📚 Reference: Larsen’s Human Embryology, 5th edition; Moore’s The Developing Human

❌ Option B: Upper limbs develop two days after lower limbs

❌ Incorrect

• It’s the opposite:

  • Upper limb buds appear first, around day 24–26.

  • Lower limb buds follow approximately 1–2 days later, around day 28.

• This is consistent with the cranio-caudal gradient of embryonic development.

❌ Option C: Limb development starts in second week of development

❌ Incorrect

• The second week is focused on bilaminar disc formation, implantation, and early trophoblast development.

• **Limb buds do not appear until the 4th week, specifically by day 24–28.

• Thus, limb development starts in the late 4th week, not the 2nd week.

❌ Option D: None of these

❌ Incorrect

• This is a trap option.

• Option A is correct, so “None of these” is wrong.

❌ Option E: Joints development starts in fourth week of development

❌ Incorrect

• Joint formation begins later, after chondrification of limb mesenchyme.

• This usually starts around the 6th week when interzones form between cartilage models, which later become joints.

• By 8th week, joint cavities begin to appear.

The digits would be connected by webbing, and would not be separated

• Apoptosis (programmed cell death) plays a crucial role in sculpting developing structures.
• In the limb bud, apoptosis occurs in the interdigital mesenchyme → this allows separation of the digits.
• If apoptosis fails, the digits remain fused by soft tissue → a condition known as syndactyly.
• Thus, failure of apoptosis doesn’t stop bone or muscle formation, but it prevents proper separation of structures that need sculpting.

❌ Bone and muscle would not form

• Formation of bone (via endochondral ossification) and muscle (from myoblasts) does not depend on apoptosis.
• These rely on mesodermal differentiation.

❌ Overlying epidermis would not form

• Epidermis is derived from ectoderm, not apoptosis-dependent.

❌ Proximal-distal patterning would not occur normally

• Proximal-distal patterning is regulated by the AER (Apical Ectodermal Ridge) and FGF signals, not apoptosis.

❌ All bones would form as the same structure

• Bone identity (humerus vs radius/ulna vs digits) is determined by HOX genes and limb bud signaling (AER, ZPA), not apoptosis.

• Limb muscles do not belong to the primaxial domain.

• Instead, they originate from the abaxial domain (ventrolateral cells of somites that migrate into the limb buds).

• The primaxial domain contributes to muscles close to the neural tube (e.g., deep back muscles, intercostals).

• Thus, saying limb muscles belong to the primaxial domain is incorrect.

🔴 Why the others are correct

• Patterning of limb muscles is controlled by connective tissue derived from parietal layer → True, the parietal (somatic) layer of lateral plate mesoderm directs limb muscle patterning.

• Innervated by ventral primary rami → True, limb muscles are supplied by ventral rami of spinal nerves (e.g., brachial and lumbosacral plexuses).

• Paraxial mesoderm will form muscles → True, muscle progenitors originate from paraxial mesoderm (somites).

• Develop from ventrolateral edge of somites → True, specifically from the ventrolateral lip of the dermomyotome, which migrates into limb buds to form muscle.

The scapula, a flat bone of the shoulder girdle, begins its development through endochondral ossification (with some intramembranous contribution at the edges). The primary ossification center is the first site where bone starts replacing cartilage, and this is a key developmental milestone.

For the scapula, the primary ossification center appears at approximately 8 weeks in utero. This occurs in the body of the scapula and marks the beginning of hard bone formation from the initial cartilaginous model.

This timing places it at the end of the embryonic period, right at the transition into the fetal period—when many of the basic structures are already formed and organ systems begin maturing.

❌ Why the Other Options Are Incorrect:

At puberty – Secondary ossification centers (like those in the acromion, coracoid process, etc.) may appear around puberty, but the primary ossification center always appears much earlier—during fetal development.

During organogenesis – Organogenesis occurs between weeks 3 to 8 of embryonic development. While this seems close, the ossification center specifically appears near the end of this window—not throughout it.

5 weeks in utero – This is too early. At this point, mesenchymal condensations and chondrification are just beginning, and the limb buds are still differentiating. Ossification has not yet begun.

At birth – By birth, the primary ossification center has long been established. However, secondary ossification centers (like those in the coracoid or acromion) are still developing postnatally.

Week 5 ✅

Hand plates form during the 5th week of embryonic development. At this stage, the upper limb buds, which appeared in the 4th week, flatten distally to form paddle-like structures — the early hand plates. These later develop digital rays in the following week (week 6).

Option-by-Option Breakdown

• Week 4 ❌
  Only limb buds appear around day 26–28. They look like small flipper-like protrusions, not yet flattened into plates.

• Week 5 ✅
  Limb buds enlarge, and the distal ends flatten into hand plates. This is the correct answer.

• Week 7 ❌
  By this stage, digital rays are well-defined and notches begin forming, but the plates themselves were already established earlier.

• Week 8 ❌
  By week 8, the fingers are distinct and separated, not merely hand plates.

• Week 9 ❌
  By week 9, digits are already formed and separated; refinement continues, not initial plate formation.

Cartilage is a type of connective tissue, and all connective tissues in the body develop from the mesoderm, one of the three primary germ layers formed during embryonic development.

More precisely, cartilage arises from mesenchymal cells, which are multipotent stem cells derived from the mesoderm. These cells have the potential to differentiate into various connective tissues, including bone, cartilage, fat, blood, and muscle.

During development, mesenchymal cells condense and differentiate into chondroblasts, which begin secreting the extracellular matrix that characterizes cartilage. Once embedded in this matrix, these cells mature into chondrocytes, the permanent cartilage cells.

There is an interesting exception — some cartilage in the head and neck region, particularly those derived from the pharyngeal (branchial) arches, is formed from neural crest cells, which come from the ectoderm. However, these neural crest cells migrate and behave like mesenchyme (ectomesenchyme), functionally acting as mesoderm-derived tissue. Despite this exception, in embryology, cartilage is categorized overall as originating from the mesoderm.

Thus, the correct answer is mesoderm.

🔍 Why the Other Options Are Incorrect:

• Epithelium refers to a type of tissue, not a germ layer. While some epithelial tissues are derived from ectoderm, mesoderm, or endoderm, cartilage is a connective tissue, not epithelium.
• Ectoderm primarily forms the skin, nervous system, and neural crest derivatives. While neural crest cells contribute to some craniofacial cartilage, the primary source of cartilage for the body is the mesoderm.
• Proctoderm is a trick option. It refers to the proctodeum, an ectodermal invagination that contributes to the formation of the lower part of the anal canal. It is not a germ layer and has no relation to cartilage.
• Endoderm forms the linings of the gastrointestinal tract, respiratory system, and various glands, but it does not contribute to connective tissues like cartilage.

Cartilage is a specialized form of connective tissue. Like all connective tissues, it is derived from the mesoderm, one of the three primary germ layers formed during embryogenesis.

Mesenchymal cells, which are multipotent cells of mesodermal origin, condense and differentiate into chondroblasts. These chondroblasts then begin secreting extracellular matrix and become trapped in it, turning into chondrocytes — the mature cells of cartilage.

Let’s break down the options:

• Epithelium – Incorrect. Epithelium arises mostly from ectoderm or endoderm, not mesoderm. It’s not related to the origin of cartilage.
• Mesoderm – ✔️ Correct. The mesoderm gives rise to bones, muscles, connective tissues (including cartilage), blood, and more.
• Ectoderm – Incorrect. This layer forms the nervous system and skin but not connective tissues like cartilage.
• Proctoderm – Incorrect. This is an outdated/ambiguous term not typically used in embryology.
• Endoderm – Incorrect. This layer gives rise to the lining of the gastrointestinal and respiratory tracts and associated organs like the liver and pancreas, but not connective tissue.

During the 7th week of embryonic development, the limbs undergo rotation:

• Upper limbs rotate laterally (so the elbows point dorsally and the extensor muscles come to lie on the posterior side).

• Lower limbs rotate medially (so the knees point ventrally and the extensor muscles come to lie on the anterior side).

This opposite rotation explains why the flexor and extensor compartments of the upper and lower limbs are arranged differently.

Option-by-Option Breakdown

• Week 4 ❌
  Only small limb buds appear; no rotation yet.

• Week 5 ❌
  Hand and foot plates begin to form, but rotation does not occur.

• Week 6 ❌
  Digital rays appear and notching begins, but the limbs are still straight.

• Week 7 ✅
  Critical week when rotation of limbs occurs, producing the definitive anatomical orientation.

• Week 9 ❌
  By this stage, rotation is already complete, and the limbs are refining in proportion and detail.

✅ Correct Answer: Amelia

Amelia is the complete absence of a limb, resulting from early disruption in limb bud development during embryogenesis (typically before 4th week of gestation). It can affect upper or lower limbs and is often due to genetic mutations or teratogenic exposures (e.g., thalidomide).

❌ Why the other options are wrong:

• Phocomelia:
  The proximal part of the limb (e.g., humerus/femur) is absent, but hands or feet are present and attached close to the trunk, like flippers.

• Micromelia:
  Refers to abnormally small limbs, where all segments are present but underdeveloped.

• Meromelia:
  Means partial absence of a limb—some segments are formed, others are missing.

• Dysmelia:
  A general term for any limb malformation, including shortened, malformed, or absent parts.

Primary ossification centers in long bones appear during fetal life, when mesenchymal cells differentiate into chondrocytes and then into osteoblasts. This process begins in the diaphysis (shaft) of long bones. The typical timing for the first appearance of these centers is around the 12th week of intrauterine life. These centers gradually ossify the shaft while the ends (epiphyses) remain cartilaginous until later.

❌ Why the other options are incorrect:

• Organogenesis period: Occurs roughly weeks 3–8, which is too early for bone ossification; only basic tissue layers are forming.

• 3rd week of intrauterine life: Too early; at this time, gastrulation and trilaminar embryo formation occur, not bone development.

• At birth: By birth, primary centers are already established; this is not when they first appear.

• Soon after birth: Secondary ossification centers appear after birth, not primary ones.

By the 7th week of embryonic development, the upper limbs bend at the elbows, and the fingers are short and slightly webbed. This is the stage just before apoptosis of the interdigital tissue, which will later (week 8) separate the fingers completely.

Option-by-Option Breakdown

• Week 4 ❌
  Limb buds have only just appeared; no bending or finger formation yet.

• Week 5 ❌
  Hand plates are formed, but no fingers or bending at the elbow yet.

• Week 6 ❌
  Digital rays appear, and notches begin to form, but the elbow is not yet flexed and fingers are still rudimentary.

• Week 7 ✅
  Classic stage: limb bending at the elbow + fingers present but webbed.

• Week 9 ❌
  By this time, digits are already fully separated and elongated. The elbow bend has already been established earlier.

🔬 What Are Somites?

• Somites are segmented blocks of paraxial mesoderm that appear along the sides of the neural tube during early embryogenesis.
• They give rise to:
  • Sclerotome → vertebrae and ribs
  • Myotome → skeletal muscles
  • Dermatome → dermis of the skin

Somites are classified based on their position:

• Preotic (in front of the otic placode/ear)
• Occipital
• Cervical
• Thoracic
• Lumbar, etc.

👁️ Development of External Ocular Muscles

• The external ocular muscles (also called extraocular muscles) are derived from preotic somites.
• These include:
  • Superior rectus
  • Inferior rectus
  • Lateral rectus
  • Medial rectus
  • Superior oblique
  • Inferior oblique
  • Levator palpebrae superioris

These muscles are innervated by cranial nerves:

• CN III (oculomotor)
• CN IV (trochlear)
• CN VI (abducens)

These cranial nerves originate from the brainstem, consistent with the preotic location of the somites.

❌ Why the Other Options Are Incorrect

Cervical somites

• Give rise to neck muscles and parts of the diaphragm (via the phrenic nerve), not eye muscles.

Occipital somites

• Contribute to tongue muscles (via the hypoglossal nerve, CN XII), not eye muscles.

Thoracic somites

• Form intercostal muscles and contribute to vertebral column, not involved in ocular muscle formation.

Lumbar somites

• Form abdominal wall muscles and lower back musculature, no role in eye development.

Digital rays — the precursors of fingers and toes — first appear in the hand plates during the 6th week of embryonic development. At this stage, the tissue between the rays is still webbed. Apoptosis later clears these webs to separate the digits.

Option-by-Option Breakdown

• Week 5 ❌
  The hand plate forms by week 5, but no distinct digital rays are visible yet. The limb bud is more paddle-like.

• Week 6 ✅
  Digital rays appear in the hand plate as condensations of mesenchyme. This is the earliest sign of finger development.

• Week 7 ❌
  By week 7, notches between digital rays deepen, and the digits are short and webbed — but the rays themselves have already formed earlier.

• Week 8 ❌
  By week 8, the interdigital webbing disappears through apoptosis, leaving fully separated fingers and toes.

• Week 9 ❌
  By this stage, digital separation is already complete, and further refinement occurs — not initial appearance.

The correct answer is: Paraxial mesoderm

Why is This the Correct Answer?

Somites are paired, segmented blocks of mesoderm that form along the neural tube during embryonic development. They arise specifically from the paraxial mesoderm, which is the thickened mesodermal tissue located on either side of the neural tube.

Somites play a crucial role in forming:

• Sclerotome → Vertebrae and ribs

• Dermatome → Dermis of the skin (back)

• Myotome → Skeletal muscles (back, limbs, body wall)

Thus, the paraxial mesoderm is essential for the development of the axial skeleton, skeletal muscles, and dermis.

Why Are the Other Options Incorrect?

1. Lateral plate mesoderm (Incorrect)

   • The lateral plate mesoderm forms the circulatory system, limb skeleton, and body wall structures.

   • It does not give rise to somites.

2. Endoderm (Incorrect)

   • The endoderm forms the epithelial lining of the gastrointestinal tract, lungs, and associated organs (liver, pancreas, thyroid, etc.).

   • It has no role in musculoskeletal development.

3. Neural crest cells (Incorrect)

   • Neural crest cells originate from the ectoderm, contributing to peripheral nerves, facial cartilage, pigment cells, and adrenal medulla.

   • They do not form somites or muscle tissues.

4. Ectoderm (Incorrect)

   • The ectoderm gives rise to the nervous system, epidermis, and neural crest derivatives.

   • It does not form mesodermal structures like somites.

Pharyngeal arches are derived from mesodermal tissue and neural crest cells, specifically from the first six cranial (head) somites, although the 5th arch is rudimentary or absent in humans.

• The first 6 somite pairs (called occipital somites) give rise to the mesodermal core of each pharyngeal arch.

• These somites migrate to populate the arches and differentiate into skeletal muscles of the head and neck.

❌ Why Other Options Are Incorrect:

• 1–3: Too limited; only includes part of the contribution.

• 3–6: Excludes the crucial 1st and 2nd arches (which form structures like the mandible and hyoid).

• 3–12: Includes somites that are too caudal and unrelated to pharyngeal arch development.

• 1–10: Includes extra somites that contribute to other regions like the tongue, neck, and trunk muscles—not pharyngeal arches.

Professor-style Explanation:

• The lateral plate mesoderm splits into two layers:

  • Somatic (parietal) mesoderm → body wall, limbs, dermis, parietal pleura/peritoneum.

  • Splanchnic (visceral) mesoderm → cardiac muscle, smooth muscle of gut, blood vessels, visceral pleura/peritoneum.

• Cardiac muscle specifically develops from the splanchnic mesoderm around the primitive heart tube.

• Why not others?

  • Somatic mesoderm → forms skeletal elements of the limbs, connective tissue of body wall.

  • Paraxial mesoderm → somites → skeletal muscle, dermis, vertebrae.

  • Intermediate mesoderm → kidneys and gonads.

  • Lateral plate mesoderm (general term) is true, but the exam expects the more precise “splanchnic mesoderm.”

✅ Correct Answer:

Formation of structures proximal to apical ridge, no formation of new distal structures

Explanation:

• The Apical Ectodermal Ridge (AER) is a thickened ectoderm at the tip of the limb bud.
• It secretes FGF (Fibroblast Growth Factors), which maintain the progress zone of mesenchymal cells in an undifferentiated, proliferative state.
• As long as the AER is present, mesenchymal cells keep proliferating and contribute to distal limb structures (e.g., fingers, toes).
• If the AER is removed:
  • Proximal structures (e.g., humerus, femur) that already began development will still form.
  • But new distal structures cannot form, leading to truncated limbs.

❌ Degeneration of limb bud

• Removal of AER does not cause complete degeneration of the limb bud.
• Proximal parts still develop normally.

❌ Regeneration of entire limb bud from underlying mesoderm

• Mammals cannot regenerate an entire limb from mesoderm once AER is removed.
• Proximal structures already specified will continue to develop, but distal regeneration does not occur.

❌ Regeneration of new AER

• In mammals, a lost AER does not regenerate.
• Some regeneration is possible in lower vertebrates (like salamanders), but not in humans.

❌ Continued development in progress zone

• The progress zone requires signals from the AER.
• Without the AER, progress zone mesenchyme differentiates prematurely, halting distal outgrowth.

✅ Correct Answer:

Paraxial mesoderm

Explanation:

• During embryonic development, the intraembryonic mesoderm organizes into three main parts on either side of the notochord:
  • Paraxial mesoderm → forms somites
  • Intermediate mesoderm → forms urogenital system
  • Lateral plate mesoderm → splits into somatic and splanchnic layers (body wall, heart, vessels, etc.)
• The paraxial mesoderm segments into somites → which later differentiate into:
  • Sclerotome → vertebrae & ribs
  • Myotome → skeletal muscles of trunk & limbs
  • Dermatome → dermis of the back

Thus, somites are the foundation of the segmental organization of the body.

❌ Endoderm

• Forms epithelial lining of GI tract, lungs, liver, pancreas, etc.
• Not musculoskeletal structures.

❌ Ectoderm

• Forms epidermis, nervous system, neural crest cells.
• No somites.

❌ Lateral plate mesoderm

• Forms body wall, heart, blood vessels, connective tissues of viscera.
• Not segmental, and not somites.

❌ Neural crest

• Migratory cells from ectoderm.
• Give rise to melanocytes, sensory ganglia, Schwann cells, adrenal medulla, craniofacial cartilage.
• Not somites.

• Long bones (like femur, tibia, humerus) grow in length by the activity of the epiphyseal (growth) plate.

• The cartilage in the growth plate undergoes interstitial growth, meaning the cartilage expands from within as new chondrocytes form and secrete matrix.

• This cartilage is then replaced by bone via endochondral ossification, which adds to the length of the bone.

🔴 Why the others are wrong

• Endochondral deposition of bone → Correct process of bone formation, but not the mechanism that allows growth in length.

• Removal of calcified cartilage → Happens during ossification but by itself does not contribute to lengthening.

• Appositional deposition of bone tissue → Responsible for increase in thickness/diameter, not length.

• Interstitial growth of bone tissue → Bone cannot grow interstitially because of its rigid mineralized matrix.

• Apoptosis (programmed cell death) is critical in embryological development.
• In limb development, apoptosis removes the interdigital tissue (the webbing between fingers and toes).
• If apoptosis fails → the tissue persists → syndactyly (fused/webbed digits).

Why the other options are incorrect

• All bones would form as the same structure
  ❌ Bone patterning depends on Hox genes and signaling pathways (not apoptosis).
• The proximo-distal patterning would not occur normally
  ❌ Controlled by apical ectodermal ridge (AER) and fibroblast growth factors (FGFs), not apoptosis.
• The bones and muscles would not form
  ❌ That would be due to failure of mesodermal differentiation, not apoptosis.
• The overlying epidermis would not form
  ❌ Epidermis derives from ectoderm, not related to apoptosis failure.

Week 8 ✅

By the 8th week (around day 56) of embryonic development, the fingers and toes become distinct and completely separated. Before this, the digits initially form as digital rays (week 6) and remain webbed (week 7). Apoptosis of the interdigital tissue during week 7–8 leads to full separation by the end of week 8.

Option-by-Option Breakdown

• Week 4 ❌
  At this stage, limb buds are only beginning to appear. No digital structures are formed yet.

• Week 5 ❌
  The upper limb bud becomes paddle-like and the hand plate forms. However, no digits are visible.

• Week 6 ❌
  Digital rays appear in the hand plate, but they are still connected by webbing. Separation has not yet occurred.

• Week 8 ✅
  Apoptosis removes the webbing between digits, and the fingers and toes are fully distinct and separated.

• Week 9 ❌
  By this stage, the separation process is already complete. Week 9 is more about further refinement and growth, not initial digit separation.

✅ Achondroplasia

• Correct statement: It is the most common cause of disproportionate (short-limb) dwarfism.
• It is due to a mutation in the FGFR3 gene, which inhibits endochondral ossification, affecting long bone growth.
• Patients have normal intelligence, a normal-sized trunk, and shortened limbs.

❌ Incorrect Options Explained:

• Osteopetrosis is characterized by lesser bone mass
  → Incorrect. Osteopetrosis, or “marble bone disease”, is actually characterized by abnormally dense but brittle bones due to defective osteoclast-mediated bone resorption.
• Thanatophoric dysplasia is harmless
  → Incorrect. The word “thanatophoric” means “death-bearing”. This severe form of skeletal dysplasia is lethal in the perinatal period due to respiratory failure from a small thoracic cavity.
• Osteoporosis is marked by denser bone
  → Incorrect. Osteoporosis is a condition of reduced bone mass and microarchitectural deterioration, leading to fragility and fractures. Bones are less dense, not more.
• Osteopetrosis is brittle bone disease
  → Incorrect. Brittle bone disease is another name for osteogenesis imperfecta, not osteopetrosis. While osteopetrosis bones can fracture easily, the underlying pathophysiology and cause are different.

✅ Correct Answer: Phocomelia

Correct Answer:

Phocomelia refers to a congenital condition where the proximal portions of a limb (like the humerus or femur) are absent, and only the distal parts (like hands or feet) are present, often rudimentary and attached close to the trunk — giving a “flipper-like” appearance, resembling a seal’s flippers.

❌ Why the other options are incorrect:

• Micromelia ❌
  → Abnormally short limbs, but all parts (proximal and distal) are present.

• Dysmelia ❌
  → A broad term for any congenital abnormality of a limb — not specific to proximal absence.

• Amelia ❌
  → Complete absence of a limb — no proximal or distal parts.

• Meromelia ❌
  → Partial absence of a limb, could be any segment — not specifically proximal absence with rudimentary distal.

During the second week of development, extraembryonic mesoderm develops between the exocoelomic membrane (Heuser’s membrane) and the cytotrophoblast. This layer later contributes to structures such as the chorionic villi and forms part of the chorion. It surrounds the amniotic cavity, yolk sac, and developing embryo.

✅ Exocoelomic membrane and cytotrophoblast — Correct. Extraembryonic mesoderm forms between these two layers.

❌ Extraembryonic membrane and cytotrophoblast — The term “extraembryonic membrane” is vague here and does not precisely describe the layers involved.

❌ Syncytiotrophoblast and cytotrophoblast — These are adjacent layers of trophoblast with no mesoderm between them.

❌ Extraembryonic membrane and syncytiotrophoblast — Again imprecise, and extraembryonic mesoderm does not lie between these layers.

❌ None of these — Incorrect, as the correct pairing is listed in the options.

The correct answer is: “The digits would be connected by webbing, and would not be separated.”

Why is This the Correct Answer?

Apoptosis, or programmed cell death, plays a crucial role in embryonic development, including the separation of digits (fingers and toes).

• During limb development, the hands and feet initially form as paddle-like structures.

• Apoptosis occurs in the interdigital mesenchyme (the tissue between the developing fingers and toes).

• If apoptosis fails, the webbing remains, leading to a condition called syndactyly (fused or webbed digits).

Thus, failure of apoptosis results in digits remaining connected by webbing instead of being fully separated.

Why Are the Other Options Incorrect?

1. “All bones would form as the same structure” (Incorrect)

   • Bone differentiation is controlled by genetic signaling pathways (e.g., HOX genes, BMPs, FGF signaling), not apoptosis.

   • Apoptosis helps shape structures but does not determine whether all bones form identically.

2. “The proximo-distal patterning would not occur normally” (Incorrect)

   • Proximo-distal (shoulder-to-finger) limb patterning is primarily regulated by the apical ectodermal ridge (AER) and FGF signaling, not apoptosis.

   • Failure of apoptosis would affect digit separation, but not overall limb segmentation.

3. “The bones and muscles would not form” (Incorrect)

   • Bone and muscle formation depend on mesenchymal condensation and differentiation, regulated by genes like Pax3, MyoD (muscles), and Sox9, Runx2 (bones).

   • Apoptosis removes unnecessary cells, but it does not initiate bone or muscle formation.

4. “The overlying epidermis would not form” (Incorrect)

   • The epidermis forms from ectodermal differentiation, controlled by Wnt, BMP, and SHH signaling.

   • Apoptosis does not play a direct role in generating the epidermis itself.

✅ Correct Answer: Meromelia

Meromelia refers to the partial absence of a limb. In this case, since the forearm is missing but the rest of the limb might be intact (e.g., hand or arm), it is a classic presentation of meromelia.

❌ Why the other options are incorrect:

• Micromelia:
  This is when the entire limb is present but abnormally small or shortened. Not absent.

• Amelia:
  This is the complete absence of a limb—none of the segments (upper arm, forearm, hand) are formed.

• Phocomelia:
  The proximal segments (like humerus) are missing, but hands or feet are attached close to the trunk, resembling flippers.

• Dysmelia:
  This is a broad, umbrella term for any congenital limb abnormality—doesn’t specify which segment is missing.

🔹 What is Syndactyly?

• “Syn” = together, “dactyly” = digits

• It refers to congenital fusion of two or more fingers or toes.

• Can involve:

  • Only soft tissues (simple syndactyly)

  • Or both bones and soft tissues (complex syndactyly)

• Occurs due to failure of apoptosis (programmed cell death) in the interdigital web spaces during embryogenesis.

Normally, digits separate by week 8 of development. If apoptosis fails — syndactyly results.

❌ Why the Other Options Are Incorrect:

. Brachydactyly

• “Brachy” = short, “dactyly” = digits

• Refers to abnormally short fingers or toes due to underdevelopment of bones.

• ❌ Not related to fusion

. Synpolydactyly

• A combination of syndactyly + polydactyly: extra digits that are fused with neighboring ones.

• Very rare, usually genetic (HOXD13 mutation).

• ❌ Close but not pure syndactyly — it involves extra digits as well

. Polydactyly

• “Poly” = many

• Presence of extra fingers or toes, often unilateral or bilateral.

• ❌ Increased number, not fusion

. None of these

• ❌ Incorrect — “syndactyly” is absolutely the correct, well-established term.

🧬 Bonus Clinical Note:

• Syndactyly is often isolated, but can also be part of syndromes like:

  • Apert syndrome

  • Poland syndrome

  • Carpenter syndrome

✅ Correct Answer:

Somatic lateral plate mesoderm

Explanation:

• Bones of the appendicular skeleton (pectoral girdle, pelvic girdle, and limb bones) are derived from the somatic (parietal) layer of lateral plate mesoderm.
• The scapula, being part of the pectoral girdle, is therefore mesodermal in origin from this layer.
• These mesodermal cells undergo chondrification first and later ossify through endochondral ossification.

❌ Neural crest cells

• Give rise to craniofacial bones, cartilage, and connective tissue, especially in the head and neck region.
• They do not contribute to scapula formation.

❌ Splanchnic lateral plate mesoderm

• Forms the heart, blood vessels, and connective tissue of the gut and viscera.
• Not involved in scapula development.

❌ Axial mesoderm

• This refers to the notochord, which induces neural tube development and forms the nucleus pulposus of intervertebral discs.
• Not related to bone formation.

❌ Somatic mesoderm (without specifying lateral plate)

• A vague option, but embryologically, “somatic” in bone context refers specifically to the somatic layer of lateral plate mesoderm.
• To be precise, the correct term is somatic lateral plate mesoderm.