Role of cell adhesions in neural development: Difference between revisions

Revision as of 02:55, 2 September 2015

Revision as of 19:11, 11 February 2016

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===Growth cone extensions===

[[Growth cone]]s function as structural and chemically sensitive axon directing cellular organelles. Growth cones are highly dynamic in nature and contain a dynamic actin cytoskeleton in their peripheral region undergoing a constant retrograde flow. This retrograde force provides a mechanism for the growth cone to respond to direction cue, thereby directing neuronal axons. Growth cones are known to respond to various mechanical cues, which may be vital in proper nervous system development as growth cones experience a wide variety of mechanical environments as they navigate the extracellular space. Interestingly, research suggest that growth cones from different regions of the brain may respond to mechanical cues differently. It has been demonstrated that neural cells located in the hippocampus aren't sensitive to varying mechanical stiffness as it related to outgrowth, where cells originating from the dorsal root ganglion show maximal outgrowth on surfaces of approximately 1 kPa. Both hippocampal and dorsal root ganglion neural growth cones show increased traction force generation on increased stiffness substrates.<ref>{{cite journal|last=Koch|first=Daniel|title=Strength in the Periphery: Growth Cone Biomechanics and Substrate Rigidity Response in Peripheral and Central Nervous System Neurons|journal=Biophysical Journal|date=February 2012|pages=452–460|doi=10.1016/j.bpj.2011.12.025 |volume=102}}</ref> Growth cones utilize integrin migratory machinery such as integrins, but are not a class of cell migration.

===Thy-1 adhesion protein===

Thy-1 (or [[thy-1|CD90.2]]) is a membrane bound [[glycoprotein]] that has been shown to be involved in the [[axon guidance]] pathway. This protein has been shown to be highly mobile, as it contains a [[Glycophosphatidylinositol|GPI]] membrane anchor. Although much of the details are elusive, it is known that thy-1 interacts with the protein dimer integrin found on [[astrocytes]], forming aggregates that can inhibit neurite outgrowth and extension. Thy-1 has also been shown to have involvement in the [[src (gene)|src]]-family kinase pathway.<ref>{{cite journal|last=Rege|first=Tanya|title=Thy-1, via its GPI anchor, modulates Src family kinase and focal adhesion kinase phosphorylation and subcellular localization, and fibroblast migration, in response to thrombospondin-1/hep I|journal=Chronology|year=2006|doi=10.1016/j.yexcr.2006.07.029|volume=312|pages=3752–3767}}</ref> This astrocyte-neuron feedback has been proposed as a mechanism involved in CNS tissue repair post-injury, as a down regulation of thy-1 may lead to enhanced neurite outgrowth. Additional research has shown that thy-1 expression in post natal humans is elevated for several weeks. This suggests that in addition to tissue repair, thy-1 might have roles in early CNS tissue development and organization.<ref>{{cite journal|last=Herrera-Molina|first=Rodrigo|title=Astrocytic aVb3 Integrin Inhibits Neurite Outgrowth and Promotes Retraction of Neuronal Processes by Clustering Thy-1|journal=PLoS ONE|date=May 2012|volume=7|series=3|pages=e34295|doi=10.1371/journal.pone.0034295|display-authors=etal}}</ref><ref>{{cite journal|last=Barker|first=Thomas|title=Thy-1 regulates fibroblast focal adhesions, cytoskeletal organization and migration through modulation of p190 RhoGAP and Rho GTPase activity|journal=Experimental Cell Research|year=2004|volume=295|pages=488–496|doi=10.1016/j.yexcr.2004.01.026 }}</ref>

===L1 family protein===

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==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 |vauthors=Ruiz JC, Cuppens H, Legius E, etal |title=Mutations in L1-CAM in two families with X linked complicated spastic paraplegia, MASA syndrome, and HSAS |journal=Journal of medicalMedical geneticsGenetics |volume=32 |issue=7 |pages=549–52 |date=July 1995 |pmid=7562969 |pmc=1050549 |doi= 10.1136/jmg.32.7.549|url=}}</ref>

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