Nerve roots have specialized transition zones that permit axon extension but limit cell movement between the CNS and PNS. Boundary cap cells prevent motor neuron soma from following their axons into the periphery, thereby contributing to a selective barrier. Transition zones also restrict movement of glial cells. Consequently, axons that cross the CNS-PNS interface are insulated by central and peripheral myelin. The mechanisms that prevent the migratory progenitors of oligodendrocytes and Schwann cells, the myelinating cells of the CNS and PNS, respectively, from crossing transition zones are not known. Here, we show that interactions between myelinating glial cells prevent their movements across the interface. Using in vivo time-lapse imaging in zebrafish we found that, in the absence of Schwann cells, oligodendrocyte progenitors cross ventral root transition zones and myelinate motor axons. These studies reveal that distinct mechanisms regulate the movement of axons, neurons, and glial cells across the CNS-PNS interface.

No abstract

Initial stages of embryonic development rely on rapid, synchronized cell divisions of the fertilized egg followed by a set of morphogenetic movements collectively called epiboly and gastrulation. Lzap is a putative tumor suppressor whose expression is lost in 30% of head and neck squamous cell carcinomas. Lzap activities include regulation of cell cycle progression and response to therapeutic agents. Here we explore developmental roles of the lzap gene during zebrafish morphogenesis. Lzap is highly conserved among vertebrates and is maternally deposited. Expression is initially ubiquitous during gastrulation, and later becomes more prominent in the pharyngeal arches, digestive tract and brain. Antisense morpholino-mediated depletion of Lzap resulted in delayed cell divisions and apoptosis during blastomere formation, resulting in fewer, larger cells. Cell cycle analysis suggested that Lzap loss in early embryonic cells resulted in a G2/M arrest. Furthermore, the Lzap-deficient embryos failed to initiate epiboly – the earliest morphogenetic movement in animal development – which has been shown to be dependent on cell adhesion and migration of epithelial sheets. Our results strongly implicate Lzap in regulation of cell cycle progression, adhesion and migratory activity of epithelial cell sheets during early development. These functions provide further insight into Lzap activity that may contribute not only to development, but also to tumor formation.

Anderson Disease (ANDD) or Chylomicron Retention Disease (CMRD) is a rare, hereditary lipid malabsorption syndrome associated with mutations in the SAR1B gene that is characterized by failure to thrive and hypocholesterolemia. Although the SAR1B structure has been resolved and its role in formation of coat protein II (COPII) coated carriers is well established, little is known about the requirement for SAR1B during embryogenesis. To address this question, we have developed a zebrafish model of Sar1b deficiency based on antisense oligonucleotide knockdown. We show that zebrafish sar1b is highly conserved among vertebrates, broadly expressed during development, and enriched in the digestive tract organs, brain and craniofacial skeleton. Consistent with ANDD symptoms of chylomicron retention, we found that dietary lipids in Sar1b deficient embryos accumulate in enterocytes. Transgenic expression analysis revealed that Sar1b is required for growth of exocrine pancreas and liver. Furthermore, we found abnormal differentiation and maturation of craniofacial cartilage associated with defects in procollagen II secretion, and absence of select, neuroD-positive neurons of the midbrain and hindbrain. The model presented here will help to systematically dissect developmental roles of Sar1b and to discover molecular and cellular mechanisms leading to organ-specific ANDD pathology.