Neural crest in development and repair
Year: 2007
Type: dissertation
Abstract: This thesis is focused on several aspects of neural crest biology,\nlargely related to two main issues: 1) understanding its mechanisms of\nmigration and 2) analyzing the potential of neural crest stem cells or\ntheir derivatives for nervous system repair. If repair is the aim,\nknowledge of both timing and events leading to axonal degeneration is\nrequired in order to block it and/or increase regeneration outcome. In\nthese studies I have made use of mouse, rat and chicken in vivo and in\nvitro models to address specific questions regarding the scope of this\nthesis.\n\nIn paper I, changes in distribution of myelin proteins are described\nafter ligation of the sciatic nerve, an injury model which does not allow\nnerve regeneration to occur. Clustering of MBPs and P0 (the two most\nabundant peripheral myelin proteins) was shown to precede their\ndegradation, involving subsequent roles of Schwann cells (SCs) and\nmacrophages in the removal of debris distally to the injury zone. Both\nclustering and protein degradation steps were found to be accelerated in\nyoung rat animals when compared to adult ones.\n\nIn paper II, similar kind of studies were applied in other two injury\nmodels allowing regeneration to occur: a transient compression (crush) of\nthe nerve or an intraneural injection of colchicine, which transiently\nblocks axonal transport. Changes in distribution of myelin (MBPs) and\naxonal (PGP9.5) protein immunoreactivities were monitored for up to one\nmonth and degeneration/regeneration processes followed and compared in\nthe two models. By applying the trophic factor apotransferrin we were\nable to block the degeneration produced by colchicine, likely through\nstabilization of axonal and/or SC cytoskeleton.\n\nIn paper III, original culture protocols have been applied to efficiently\ngenerate highly pure cultures of mature SCs from boundary cap neural\ncrest stem cells (bNCSCs). The in vitro SC differentiation from stem\ncells was found to resemble the in vivo process when looking at\ncombinations of markers changing expression during SC lineage. Stem\ncell-derived SCs were able to myelinate axons both in vitro and in vivo.\nThese results prompted further work shown in paper V, in which the\nregenerative potential of neural crest stem cell-derived SCs has been\ntested in the contused spinal cord injury model. Even though in most\ncases grafted cells died soon after transplantation, when grafted alive\nthey were found to improve locomotor behavior and to enhance endogenous\nregenerative mechanisms, producing both an increase in axonal re-growth\nand in recruitment of endogenous glial cells. In this study, evidences\nare shown suggesting that after injury ependymal cells of the spinal cord\ncentral canal can generate endogenous glial cells of myelinating\nphenotype, likely including some of the Schwann like cells which populate\nthe injury zone allowing axonal re-growth.\n\nIn paper IV, the scaffolding protein Nedd9 is shown to be expressed by\nmultipotent migrating and post-migratory neural crest cells (NCCs). Nedd9\nexpression is induced in NCCs at the level of the dermamyotome dorsal\nlip. Loss-of-function and gain-offunction studies were consistent with a\nprincipal role for Nedd9 in NCC migration. Retinoic acid, known to be\nsynthesized by the dermamyotome, was found to induce Nedd9 expression in\nNCCs. Nedd9 expression pattern in mouse is described in paper VI,\nincluding mesencephalic ventral midbrain as well as other discrete\nprogenitor populations from diverse tissues and organs.
Source: Figshare
Author: Jorge B. Aquino
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W170729614