(A) Evolution of locomotor strategies. Top: A chordate phylogeny showing representative
species of tetrapods (dark purple) and vertebrates (light purple). Chondrichthyans
represent the most primitive species bearing paired appendages. Bottom: Comparisons of
locomotor behaviors in lamprey, salamander and mouse.
(B) Altered MN columnar organization in Foxp1 and Hox
mutants. In Foxp1 mutants Hox-dependent spinal MN columns (LMC and PGC)
are transformed into an HMC-like “ground state”, which may represent a
primitive condition. PMC neurons are present in Foxp1 mutants, but not
depicted. Loss of LMC neurons at brachial levels is achieved only when
HoxA and HoxC gene clusters are mutated. Lumbar LMC
neurons are preserved in HoxA/C cluster mutant mice due to Hoxd10
activity. Deletion of the Hoxc9 gene causes global derepression of
brachial Hox genes resulting in an extension of the brachial LMC
throughout thoracic levels. MMC neurons are considered Hox-independent as their molecular
profiles are preserved in each of these mutants.
(C) A model showing how MN organization has evolved with changes in body plans. A subset
of MNs in agnathan vertebrates (represented by modern lampreys) may have lost Lhx3
activity, permitting the generation of HMC-like neurons. The acquisition of
paired-appendages promoted the generation of LMC-like populations, which may have been
initially present at most spinal levels. A repressive domain within Hox9 proteins
necessary to suppress LMC specification appears to have emerged when the elongate fin
split into pectoral and pelvic fins. Studies in zebrafish suggest the pectoral fin MNs
were initially positioned in both the hindbrain (HB) and spinal cord (SC) (Ma et al., 2010). Pelvic fin innervating MNs do not align with
Hox10 gene expression (Murata et al.,
2010). In mammals, PMC neurons are specified by Hox5 proteins and are
Foxp1-independent (Philippidou et al., 2012).
(D) In snake embryos expansion of Hoxc9 expression blocks LMC
generation. The enlarged-finned fish skate, which naturally has lost the
HoxC cluster, may have extended LMC population along the
anteroposterior axis of the spinal cord.