Role of cell adhesions in neural development: Difference between revisions

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===L1 family protein===

The [[L1 family]] of proteins are involved in neuronal migration, as well as in axon growth and proper synapse formation, and include L1CAM NrCAM and neurofascin. L1-Cell Adhesion Molecule (L1CAM) was first discovered to be important in neuron-related tissue development in the mid-1980s, and is a trans-membranal glycoprotein of approximately 200-220 kDa. On its extracellular ___domain, the L1CAM protein includes [[Immunoglobulin|IgG]]-like and [[fibronectin]]-III (FN-III) repeats which allow for interaction with integrins and ECM proteins. Similarly to integrin, F1CAM expresses domains intracellularly that interact with the actin cytoskeleton. Supporting the claim that L1-family proteins are involved in CNS development is the finding that L1CAM is highly expressed in neuronal tissue during its early stages of growth, especially at the ends of axons. Some areas of the brain, such as the hippocampus, have been found to highly express L1CAM into adulthood, though the exact reason for this has not been elucidated.

Due to its involvement in neuronal development and axon guidance, itsit has been proposed that L1CAM and L1-family proteins may be useful therapeutics to treat tissue damage in the CNS. Some have even proposed that L1CAM expression is elevated in vivo during tissue repair, which would support the notion that it yields benefit during CNS tissue repair.<ref>{{cite journal|last=Schafer|first=Michael|author2=Michael Frotscher |title=Role of L1CAM for axon sprouting and branching|journal=Cell Tissue Res|date=February 2012|volume=349|pages=39–48|doi=10.1007/s00441-012-1345-4}}</ref>

===Mechanosensing in neurons===

Mechanosensing is a process by which cells alter their bio-physical properties in response to mechanical cues present in the environment. It is well known that a wide-variety of cell types change their behavior to mechanical environmental signals.

In addition to providing force transmission to the ECM for neuron extension and development, Integrin mediated adhesions are also functional in these mechanosensing processes in neurons. Sensing of the external environments mechanical properties ''in vivo'' can determine cell behaviors such as differentiation and branching. It has been experimentally determined that increasing substrate stiffness (~2-80kPa) can result in sequestered neurite branching and branch length.<ref>{{cite journal|last=Man|first=Alan|title=Neurite Outgrowth in Fibrin Gels Is Regulated by Substrate Stiffness|journal=Tissue Engineering|year=2011|volume=17|issue=23 and 24|pages=2931-1941|doi=10.1089/ten.tea.2011.0030}}</ref><ref>{{cite journal|last=Jiang|first=Frank|title=Neurite Outgrowth on a DNA Crosslinked Hydrogel with Tunable Stiffnesses|journal=Annals of Biomedical Engineering|date=September 2008|volume=36|issue=9|pages=1565–1579|doi=10.1007/s10439-008-9530-z}}</ref>

==Relevant neurological conditions==

Several debilitating diseases are brought about from errors in neural development due in part to problems involving neural cell adhesions and adhesion mechanisms.

*CRASH syndrome (or L1 syndrome) is brought about by a mutation in the L1CAM gene on the x-[[chromosome]], resulting in a malfunctioning L1CAM protein. CRASH (acronym) syndrome include the conditions:<ref name="pmid8556302">{{cite journal |author=Fransen E, Lemmon V, Van Camp G, Vits L, Coucke P, Willems PJ |title=CRASH syndrome: clinical spectrum of corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one single gene, L1 |journal=European Journal of Human Genetics |volume=3 |issue=5 |pages=273–84 |year=1995 |pmid=8556302 }}</ref><ref name="pmid7562969">{{cite journal |author=Ruiz JC, Cuppens H, Legius E, et al.|title=Mutations in L1-CAM in two families with X linked complicated spastic paraplegia, MASA syndrome, and HSAS |journal=Journal of medical genetics |volume=32 |issue=7 |pages=549–52 |date=July 1995 |pmid=7562969 |pmc=1050549 |doi= 10.1136/jmg.32.7.549|url=}}</ref>