#digit identity

Limb Development -ll

Which molecule determines digit identity in the autopod?

Autopod digit patterning and identity along anterior-posterior axis depend on posterior-derived Sonic Hedgehog gradient from ZPA. Duration and concentration of SHH exposure differentially regulate Gli3 processing from repressor to activator and 5-prime HoxD expression, specifying digit one thumb anteriorly through digit five little finger posteriorly with distinct sizes. High prolonged SHH maintains posterior Hoxd13 and posterior identity, low transient yields anterior. BMP4 sculpts interdigits through apoptosis, Wnt3a governs dorsal-ventral polarity, TBX5 governs forelimb field. Thus SHH determines which morphological digit character forms in autopod and controls number.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: SHH determines digit identity.

View Details

Limb Development -ll

Which signaling molecule is secreted by ZPA to regulate digit identity?

Zone of polarizing activity at posterior limb margin secretes Sonic Hedgehog morphogen that patterns anterior-posterior axis and imparts digit identities through graded exposure and Gli regulation. SHH concentration and duration activate differential Gli target genes and posterior HoxD cluster specifying digits 1 to 5 from anterior to posterior with distinct phalangeal formulas. Low short SHH supports thumb identity, high prolonged SHH supports posterior digits 5 and 4. FGF8 patterns proximal-distal outgrowth, BMP4 promotes apoptosis and chondrogenesis, Wnt7a patterns dorsal-ventral. Therefore ZPA-derived SHH regulates digit identity establishment fundamentally.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: ZPA secretes SHH for digit identity.

View Details

Limb Development -lll

Which factor plays a major role in regulating digit identity by controlling Sonic Hedgehog (Shh) expression?

Digit identity along anterior-posterior axis depends on graded Sonic Hedgehog from zone of polarizing activity. SHH induces Gremlin1, which antagonizes BMPs, thereby sustaining AER FGFs and forming SHH-Gremlin-FGF feedback loop that prolongs SHH exposure and expands progenitors. Higher and longer SHH promotes posterior digit fates through sustained Hoxd13 and Gli activator activity and repression of Gli3 repressor. Interruption of Gremlin alters SHH duration and range, changing digit number and morphology. TBX5 specifies forelimb field, BMP4 drives apoptosis, Wnt3a induces AER.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: ZPA SHH-Gremlin loop and digit identity.

View Details

Tetrapod

Which molecule is involved in specifying digit identity in the autopod?

Digit identity within autopod depends on anterior-posterior gradient of Sonic hedgehog duration and concentration from ZPA. High prolonged SHH posteriorly prevents Gli3 repressor formation, induces Hand2, posterior HoxD13 targets specifying posterior digits 5 and 4 with ulnar characteristics. Low SHH anterior allows Gli3R to promote digit 1 thumb identity. Manipulating SHH bead exposure time converts anterior digits to posterior fate. Gli3 mutant mice show polydactyly with loss of identity gradient. Hence SHH provides instructional positional information defining digit morphological individuality through Gli transcription factor balance and BMP interactions.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: SHH gradient and digit identity, Gli3 regulation.

View Details

Tetrapod

Which signaling molecule is secreted from the ZPA to regulate digit identity?

Posterior mesenchyme Zone of Polarizing Activity produces Sonic hedgehog which acts as long-range morphogen specifying anterior-posterior axis through concentration gradient. High levels activate Gli activator form high posteriorly, repress Gli3 repressor formation anteriorly, establishing digit identity gradient. High levels promote posterior ulnar digits expressing Hand2, intermediate specifies central digits, absence specifies anterior thumb. SHH-coated beads grafted anteriorly replicate ZPA duplication experiments producing mirror-image polydactyly. Moreover SHH induces downstream Fgf4 in AER and BMP antagonists, supporting survival and expansion of patterning domain and maintaining outgrowth coordination.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: SHH secretion from ZPA and digit identity.

View Details