Polysialylated NCAM expression during motor axon outgrowth and myogenesis in the fetal rat

Abstract

Polysialylation of the neural cell adhesion molecule (NCAM) converts it into an anti-adhesive molecule, attenuating intercellular adhesion and repelling apposed membranes. Previous studies have demonstrated that interaxonal repulsion, or defasciculation, induced by polysialylated NCAM (PSA-NCAM) expressed along outgrowing chick motor axons promotes intramuscular branching and facilitates differential guidance of segregating axonal populations. In the present study, we have examined the expression of PSA-NCAM in a developing mammalian motor system during axonal outgrowth, separation of distinct axonal populations, and intramuscular branching. Furthermore, we provide the first clear demonstration of the spatiotemporal modulation of PSA-NCAM expression on myotubes during each stage of myogenesis. Immunohistochemical labelling was used to compare the spatiotemporal pattern of PSA-NCAM expression with those of total-NCAM, the cell adhesion molecule L1, and growth associated protein (GAP-43) during development of the phrenic nerve and diaphragm of fetal rats (embryonic days, E11-E19). During segregation of phrenic and brachial axonal populations at the brachial plexus (E12.5-E13), PSA-NCAM expression was restricted to phrenics, being absent from brachial motoneurons. Both populations labelled equivalently for NCAM, L1, and GAP-43. We postulate that PSA-NCAM may be a component of the molecular machinery that specifically guides phrenic motoneuron growth at the brachial plexus. During diaphragmatic morphogenesis, PSA-NCAM expression: (i) remained high within the phrenic nerve throughout intramuscular branching; (ii) was transiently up-regulated on myotubes during myotube separation associated with primary and secondary myogenesis; (iii) was restricted to those regions of primary and secondary myotube membranes, which were juxtaposed and about to separate. These data suggest a role for PSA-NCAM in the guidance of specific subsets of mammalian motoneurons and in intramuscular branching, and demonstrate an intimate correlation between PSA-NCAM expression and myotube separation.

Gene expression in the developing diaphragm: significance for congenital diaphragmatic hernia

“…ST8SIA2 is also an interesting candidate; this gene encodes a polysialyltransferase enzyme that is thought to play a role in the polysialylation of the neural cell adhesion molecule (21). This is of interest because polysialylated neural cell adhesion molecule is thought to play a role in the guidance of the phrenic nerve to the PPF and has been shown to be differentially expressed during myotube separation in the diaphragm, although the significance of this with regard to the development of CDH is unclear, because the pathogenesis of Bochdalek CDH does not appear to be related to diaphragm myogenesis and innervation (4,5,9). Below, we discuss the expression pattern of Igf1r, Rgma, and Coup-tfII in the PPF and the significance of this with regard to CDH.…”

Down-regulation of the axonal polysialic acid–neural cell adhesion molecule expression coincides with the onset of myelination in the human fetal forebrain

“…Expression of PSA-NCAM by various progenitor cell populations in the central nervous system was reported (Gascon et al, 2007;Vitry et al, 2001;Allan and Greer, 1998;Oumesmar et al, 1995), including in vivo expression by glial restricted progenitors in the perinatal mouse subvetricular zone (Marshall and Goldman, 2002). In vitro isolated PSA-NCAM+ cells considered "oligodendrocyte pre-progenitors" (Ben-Hur et al, 1998, Decker et al, 2000 were used to give rise to both glia and neurons upon transplantation, depending on their insertion site in the developing mouse brain (Vitry et al, 2001).…”

Effect of nitrofen in the final stages of development of the diaphragm muscle in rats

“…After that, they complete segmentation of the thoracic and abdominal cavities. The evidences indicate that the PPMs are the largest, if not the only structure responsible for the development of the diaphragm muscles 5 .…”

“…MÉTODOS: Fetos de ratas foram divididos em quatro grupos: Controle Externo (EC), composto de ratas não manipuladas; Nitrofen, composto de ratas que receberam 100 mg de nitrofen (2,4-dicloro-4'nitrodifenil éter) diluído no azeite no dia de gestação (GD) 9.5, cujos fetos desenvolveram CDH (N+) ou não (N-) e Placebo óleo de oliva (OO), composto de ratas que ingeriram apenas óleo no mesmo GD. Os fetos foram coletados com 18,5, 19,5, 20,5 e 21,5 GD (termo = 22 dias). Foi obtido o peso corporal (BW) e tiradas fotografias da área do diafragma (DA), da hérnia (HA) e calculada a relação HA/DA no grupo N+.…”