Fetal development of the enteric nervous system of transgenic mice that overexpress the Hoxa-4 gene.

Megacolon occurs in neonatal and adult transgenic mice that overexpress the Hoxa-4 gene. Abnormalities, which are restricted to the terminal colon of these mice, include a hypoganglionosis, abnormal enteric ganglia with a structure appropriate for extra-enteric peripheral nerve and not the enteric nervous system (ENS), and gaps in the longitudinal muscle occupied by ganglia. To investigate the developmental origin of these abnormalities, we analyzed the development of the pelvis and terminal colon in Hoxa-4 transgenic mice.

The alpha1 subunit of laminin-1 promotes the development of neurons by interacting with LBP110 expressed by neural crest-derived cells immunoselected from the fetal mouse gut.

A plasmalemmal protein, LBP110, which binds to the alpha1 chain of laminin-1, is acquired by the neural crest-derived precursors of enteric neurons after they colonize the gut. We tested the hypothesis that laminin-1 interacts with LBP110 to promote enteric neuronal development. The effects of laminin-1 on neuronal development were studied in cultures of cells immunoselected from fetal mouse gut (E14-15) with antibodies to LBP110 or p75NTR, a marker for enteric crest-derived cells.

Distinct subpopulations of enteric neuronal progenitors defined by time of development, sympathoadrenal lineage markers and Mash-1-dependence.

Enteric and sympathetic neurons have previously been proposed to be lineally related. We present independent lines of evidence that suggest that enteric neurons arise from at least two lineages, only one of which expresses markers in common with sympathoadrenal cells. In the rat, sympathoadrenal markers are expressed, in the same order as in sympathetic neurons, by a subset of enteric neuronal precursors, which also transiently express tyrosine hydroxylase.

Structural abnormalities associated with congenital megacolon in transgenic mice that overexpress the Hoxa-4 gene.

Congenital megacolon develops in transgenic mice that overexpress the homeobox-containing gene, Hoxa-4. The current study was done to identify abnormalities of the terminal colon that might account for the phenotype. The terminal bowel of transgenic mice was compared with that of control and lethal spotted (ls/ls) mice, a strain in which megacolon also develops.

Neural crest-derived cells isolated from the gut by immunoselection develop neuronal and glial phenotypes when cultured on laminin.

The neural crest-derived cells that colonize the bowel are different from their predecessors in the premigratory crest. A procedure, which utilized the immunoselection of cells with a magnet, was thus devised to obtain crest-derived precursors from developing gut. Primary antibodies against cell surface antigens, NC-1 in chick, quail, and rat, or antibodies to a 110-kDa laminin binding protein (alpha-110) in mouse, were used in conjunction with secondary antibodies coupled to magnetic beads.