(a) What are morphogens ? Describe the cellular differentiation during morphogenesis. 20 (b) What are gap junction proteins ?…

(a) Morphogens and cellular differentiation during morphogenesis

Morphogens

• Morphogens are secreted or diffusible signalling molecules that form a concentration gradient and specify different cell fates at different thresholds, thereby giving positional information. Examples: Bicoid (anterior gradient in Drosophila, a transcription factor that is itself the gradient), Dpp/BMP, Sonic hedgehog (Shh), Wnt, FGF and retinoic acid in vertebrates.

Differentiation during morphogenesis

• Morphogenesis is the generation of form: gastrulation, neurulation, limb and organ shaping through cell movement, shape change, adhesion, proliferation and apoptosis.
• Specification: cells of a field, competent to respond, read the gradient and switch on position-specific transcription factors (e.g., high Shh specifies ventral neural-tube fates such as floor plate and motor neurons, lower levels interneurons, and its absence dorsal fates, with BMP/Wnt from the roof plate opposing it).
• Determination: fate becomes stable through gene-regulatory networks and epigenetic memory, and cells become restricted to a lineage (induction and lateral inhibition refine the pattern).
• Terminal differentiation: lineage-specific genes are expressed, giving specialised structure and function (neuron, myocyte, epithelial cell). Differential adhesion (cadherins), extracellular-matrix remodelling and programmed cell death (digit separation) shape tissues in parallel.
• Thus a homogeneous field is converted into patterned, differentiated tissues.

(b) Gap junction proteins and roles of connexins

Gap junction proteins

• Gap junctions are clusters of intercellular channels. In vertebrates the subunits are connexins (21 in humans); six connexins form a hemichannel (connexon), and two connexons of adjacent cells dock across the 2–4 nm gap to make a channel of about 1.2–1.5 nm pore, passing ions and molecules up to about 1 kDa. In invertebrates the equivalent proteins are innexins; pannexins form mainly single-membrane channels rather than classical gap junctions.

Roles of connexins

• Electrical coupling: Cx43 in cardiac muscle gives rapid, synchronised conduction and contraction; Cx36 couples neurons at electrical synapses; Cx26 and Cx30 recycle K+ in the cochlea.
• Metabolic coupling: passage of ATP, cAMP, IP3, Ca2+ and nutrients lets cells share second messengers and propagate Ca2+ waves.
• Development: coupling helps coordinate embryonic cell groups, and Cx43 is important in heart, bone and neural-crest development.
• Gating: channels are regulated by pH, Ca2+ and phosphorylation, closing to isolate damaged cells.
• Disease: Cx26 mutations cause non-syndromic deafness, Cx32 mutations cause X-linked Charcot-Marie-Tooth disease, and Cx43 mutations cause oculodentodigital dysplasia.

(c) Primordial germ cell and oogenesis

Primordial germ cells (PGCs)

• PGCs are the embryonic precursors of gametes. In humans they are specified in the posterior epiblast (BMP signalling), are found in the yolk-sac wall near the allantois, and migrate along the hindgut and dorsal mesentery to the gonadal ridges by about the fifth to sixth week.

Oogenesis (see the figure below)

• Multiplication: in the fetal ovary PGCs become oogonia, which divide mitotically (up to about 7 million by mid-gestation).
• Growth: oogonia enter meiosis I as primary oocytes before birth and arrest in diplotene of prophase I (dictyate stage), each enclosed by flat follicle cells as a primordial follicle. Many degenerate; about 1–2 million remain at birth and about 400,000 at puberty.
• Maturation: from puberty, under FSH and LH, a few follicles per cycle grow through primary, secondary (antral) and Graafian stages. Just before ovulation the LH surge makes one primary oocyte finish meiosis I, giving a large secondary oocyte and a small first polar body; the secondary oocyte then arrests at metaphase II.
• Ovulation releases the secondary oocyte; meiosis II is completed only on sperm entry, giving the ovum and a second polar body. Each oogonium thus yields one ovum and (up to) three polar bodies, which degenerate; the empty follicle forms the corpus luteum. Only about 400–500 oocytes are ovulated in a lifetime.