Zebrafish as an emerging model to study estrogen receptors in neural development.

Estrogens induce several regulatory signals in the nervous system that are mainly mediated through estrogen receptors (ERs). ERs are largely expressed in the nervous system, yet the importance of ERs to neural development has only been elucidated over the last decades. Accumulating evidence shows a fundamental role for estrogens in the development of the central and peripheral nervous systems, hence, the contribution of ERs to neural function is now a growing area of research. The conservation of the structure of the ERs and their response to estrogens make the zebrafish an interesting model to dissect the role of estrogens in the nervous system. In this review, we highlight major findings of ER signaling in embryonic zebrafish neural development and compare the similarities and differences to research in rodents. We also discuss how the recent generation of zebrafish ER mutants, coupled with the availability of several transgenic reporter lines, its amenability to pharmacological studies and in vivo live imaging, could help us explore ER function in embryonic neural development.

Pals1a and aPKCλ are not essential for Schwann cell migration, division or myelination in zebrafish.

BACKGROUND: Schwann cells (SCs) are specialized glial cells of the peripheral nervous system that produce myelin and promote fast action potential propagation. In order to myelinate, SCs engage in a series of events that include migration and division along axons, followed by extensive cytoskeletal rearrangements that ensure axonal ensheathment and myelination. SCs are polarized and extend their processes along an abaxonal-adaxonal axis. Here, we investigate the role of the apical polarity proteins, Pals1a, and aPKCλ, in SC behavior during zebrafish development. RESULTS: We analyzed zebrafish nok and has mutants deficient for pals1a and aPKCλ function respectively. Using live imaging, transmission electron microscopy and whole mount immunostaining, we show that SCs can migrate and divide appropriately, exhibit normal radial sorting, express myelin markers and ensheath axons on time in has and nok mutants. CONCLUSIONS: Pals1a and aPKCλ are not essential for SC migration, division or myelination in zebrafish.

Timely Schwann cell division drives peripheral myelination in vivo via the laminin/cAMP pathway.

Schwann cells (SCs) migrate along peripheral axons and divide intensively to generate the right number of cells prior to axonal ensheathment; however, little is known regarding the temporal and molecular control of their division and its impact on myelination. We report that Sil, a spindle pole protein associated with autosomal recessive primary microcephaly, is required for temporal mitotic exit of SCs. In sil-deficient cassiopeia (csp-/-) mutants, SCs fail to radially sort and myelinate peripheral axons. Elevation of cAMP, but not Rac1 activity, in csp-/- restores myelin ensheathment. Most importantly, we show a significant decrease in laminin expression within csp-/- posterior lateral line nerve and that forcing Laminin 2 expression in csp-/- fully restores the ability of SCs to myelinate. Thus, we demonstrate an essential role for timely SC division in mediating laminin expression to orchestrate radial sorting and peripheral myelination in vivo.

Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish.

The Regulator of G protein signaling 4 (Rgs4) is a member of the RGS proteins superfamily that modulates the activity of G-protein coupled receptors. It is mainly expressed in the nervous system and is linked to several neuronal signaling pathways; however, its role in neural development in vivo remains inconclusive. Here, we generated and characterized a rgs4 loss of function model (MZrgs4) in zebrafish. MZrgs4 embryos showed motility defects and presented reduced head and eye sizes, reflecting defective motoneurons axon outgrowth and a significant decrease in the number of neurons in the central and peripheral nervous system. Forcing the expression of Rgs4 specifically within motoneurons rescued their early defective outgrowth in MZrgs4 embryos, indicating an autonomous role for Rgs4 in motoneurons. We also analyzed the role of Akt, Erk and mechanistic target of rapamycin (mTOR) signaling cascades and showed a requirement for these pathways in motoneurons axon outgrowth and neuronal development. Drawing on pharmacological and rescue experiments in MZrgs4, we provide evidence that Rgs4 facilitates signaling mediated by Akt, Erk and mTOR in order to drive axon outgrowth in motoneurons and regulate neuronal numbers.

Rho GTPases Signaling in Zebrafish Development and Disease.

Cells encounter countless external cues and the specificity of their responses is translated through a myriad of tightly regulated intracellular signals. For this, Rho GTPases play a central role and transduce signals that contribute to fundamental cell dynamic and survival events. Here, we review our knowledge on how zebrafish helped us understand the role of some of these proteins in a multitude of in vivo cellular behaviors. Zebrafish studies offer a unique opportunity to explore the role and more specifically the spatial and temporal dynamic of Rho GTPases activities within a complex environment at a level of details unachievable in any other vertebrate organism.