During vertebrate embryogenesis, myogenic precursor cells of limb muscles
delaminate from the ventro-lateral edge of the somitic dermomyotome and migrate
to the limb buds, where they congregate into dorsal and ventral muscle masses1,
2. It has been proposed that the surrounding connective tissue
controls muscle pattern formation in limbs3,
4,
5. Regulatory
molecules such as receptor tyrosine kinases like c-Met (
ref. 6) and those encoded by homeobox-containing genes, including
c-Met (ref. 6), Tbx1 (
ref. 7), Mox2 (ref. 8), Six1
and Six2 (ref. 9), Pitx2,
Pax3 (refs 10,11)
and Lbx1h (refs 12,13), are expressed in migrating limb precursor cells.
The role of these genes in the patterning of limb muscles is unknown, although
mutation of Pax3 or Met causes disruption of limb muscle development
at an initial step, disturbing the epithelial-to-mesenchymal transition of
the somitic epithelium6,
10,
11. No limb muscle cells form in
these mutants, and the early loss of myogenic precursor cells prevented an
analysis of later functions of these genes during limb muscle development14. Based on quail-chick chimaera studies3,
15, it was
assumed that a cell-autonomous contribution of myogenic cells to the formation
of individual limb muscles is negligible, and that an instructive role of
limb mesenchyme is critical in this process. Here we show that Lbx1h
determines migratory routes of muscle precursor cells in a cell-autonomous
manner, thereby leading to the formation of distinct limb muscle patterns.
Inactivation of Lbx1h, which is specifically expressed in migrating
muscle precursor cells12,
13, led to a lack of extensor muscles
in forelimbs and an absence of muscles in hindlimbs. The defect was caused
by the failure of all muscle precursor cells of hindlimbs and of precursor
cells of extensor muscles of forelimbs to migrate to their corresponding muscle
anlagen. Our results demonstrate that Lbx1h is a key regulator of muscle
precursor cell migration and is required for the acquisition of dorsal identities
of forelimb muscles.
