Key Pattern-Forming Genes and Their Expression in Limb Buds

• Lmx1b (LIM homeobox transcription factor 1 beta):
  Expressed specifically in the dorsal mesenchyme of the limb bud, Lmx1b is essential for establishing dorsal limb identity. Mutations lead to dorsal-ventral patterning defects as seen in Nail-Patella Syndrome.

• Shh (Sonic Hedgehog):
  Shh is expressed in the posterior mesenchymal region known as the Zone of Polarizing Activity (ZPA) and is essential for anterior-posterior patterning of the limb, influencing digit identity and number.

• Wnt7a:
  Expressed in the dorsal ectoderm, Wnt7a regulates dorsal limb patterning and maintains Lmx1b expression in the dorsal mesenchyme. Defects in Wnt7a alter dorsal-ventral limb patterning.

• Hoxa13 and Hoxd13:
  These distally expressed Hox genes govern specification and patterning of the autopod—the hand and foot regions—and digit morphogenesis.

• Tbx5 and FGF10:
  Expressed in the lateral plate mesoderm, these genes are crucial early limb bud initiators. Tbx5 is specific to forelimb buds, while Tbx4 is related to hindlimb buds, both regulating FGF10 to induce limb outgrowth.

Association with Nail-Patella Syndrome and Mouse Phenotypes

• Nail-Patella Syndrome in humans is linked to mutations in the Lmx1b gene, resulting in limb dorsalization defects, including nail and patella dysplasia, highlighting Lmx1b’s key role in dorsal limb identity.

• Studies in mice demonstrate that mutants with altered dorsal-ventral patterning and aberrant expression of dorsal genes such as Lmx1b and Wnt7a exhibit footpads on both dorsal and ventral limb surfaces—an abnormality showing loss of normal dorsal-ventral limb polarity.

• The syndromes observed correlate with the functions of Lmx1b and Wnt7a (statements A and C), confirming their pivotal role in dorsal limb development.

Why Other Genes Are Less Directly Associated

• Shh (B), Hoxa13 and Hoxd13 (D), and Tbx5/FGF10 (E) are primarily involved in limb patterning along anterior-posterior or proximodistal axes or in limb initiation but are not directly involved in the dorsal-ventral patterning defects seen in these syndromes.

Summary

The Nail-Patella Syndrome in humans and mouse syndromes exhibiting dorsal and ventral footpads relate specifically to defective dorsal limb gene function. The genes responsible are Lmx1b, expressed in dorsal mesenchyme, and Wnt7a, expressed in dorsal ectoderm. These genes coordinate dorsal-ventral axis formation, and their mutation leads to characteristic limb malformations.

Final Answer:
(4) A and C only