Editing Thalamus (section)

===Maturation and parcellation of the thalamus===
After its induction, the MDO starts to orchestrate the development of the thalamic anlage by release of signalling molecules such as SHH.<ref>{{cite journal |pmid=12948657 |year=2003 |last1=Puelles |first1=L |last2=Rubenstein |first2=JL |title=Forebrain gene expression domains and the evolving prosomeric model |volume=26 |issue=9 |pages=469–76 |journal=Trends in Neurosciences |doi=10.1016/S0166-2236(03)00234-0|s2cid=14658562}}</ref> In mice, the function of signaling at the MDO has not been addressed directly due to a complete absence of the [[diencephalon]] in SHH mutants.<ref>{{cite journal |pmid=12361972 |year=2002 |last1=Ishibashi |first1=M |last2=McMahon |first2=AP |title=A sonic hedgehog-dependent signaling relay regulates growth of diencephalic and mesencephalic primordia in the early mouse embryo |volume=129 |issue=20 |pages=4807–19 |journal=Development|doi=10.1242/dev.129.20.4807}}</ref>

Studies in chicks have shown that SHH is both necessary and sufficient for thalamic gene induction.<ref>{{cite journal |pmid=15494730 |year=2004 |last1=Kiecker |first1=C |last2=Lumsden |first2=A |title=Hedgehog signaling from the ZLI regulates diencephalic regional identity |volume=7 |issue=11 |pages=1242–9 |doi=10.1038/nn1338 |journal=Nature Neuroscience|s2cid=29863625}}</ref> In [[zebrafish]], it was shown that the expression of two SHH genes, SHH-a and SHH-b (formerly described as twhh) mark the MDO territory, and that SHH signaling is sufficient for the molecular differentiation of both the prethalamus and the thalamus but is not required for their maintenance and SHH signaling from the MDO/alar plate is sufficient for the maturation of prethalamic and thalamic territory while ventral Shh signals are dispensable.<ref>{{cite journal |doi=10.1242/dev.02248 |title=Hedgehog signalling from the zona limitans intrathalamica orchestrates patterning of the zebrafish diencephalon |year=2006 |last1=Scholpp |first1=S. |journal=Development |volume=133 |issue=5 |pages=855–64 |pmid=16452095 |last2=Wolf |first2=O |last3=Brand |first3=M |last4=Lumsden |first4=A|doi-access=free}}</ref>

The exposure to SHH leads to differentiation of thalamic neurons. SHH signaling from the MDO induces a posterior-to-anterior wave of expression the proneural gene [[Neurogenins|Neurogenin1]] in the major (caudal) part of the thalamus, and Ascl1 (formerly Mash1) in the remaining narrow stripe of rostral thalamic cells immediately adjacent to the MDO, and in the prethalamus.<ref>{{cite journal |doi=10.1073/pnas.0910894106 |title=Her6 regulates the neurogenetic gradient and neuronal identity in the thalamus |year=2009 |last1=Scholpp |first1=S. |last2=Delogu |first2=A. |last3=Gilthorpe |first3=J. |last4=Peukert |first4=D. |last5=Schindler |first5=S. |last6=Lumsden |first6=A. |journal=Proceedings of the National Academy of Sciences |pmid=19903880 |pmc=2775703 |volume=106 |issue=47 |pages=19895–900|bibcode=2009PNAS..10619895S |doi-access=free}}</ref><ref>{{cite journal |first1=Tou Yia |last1=Vue |first2=Krista |last2=Bluske |first3=Amin |last3=Alishahi |first4=Lin Lin |last4=Yang |first5=Naoko |last5=Koyano-Nakagawa |first6=Bennett |last6=Novitch |first7=Yasushi |last7=Nakagawa |title=Sonic Hedgehog Signaling Controls Thalamic Progenitor Identity and Nuclei Specification in Mice |doi=10.1523/JNEUROSCI.0656-09.2009 |year=2009 |journal=Journal of Neuroscience |volume=29 |issue=14 |pages=4484–97 |pmid=19357274 |pmc=2718849}}</ref>

This zonation of proneural gene expression leads to the differentiation of glutamatergic relay neurons from the Neurogenin1+ precursors and of GABAergic inhibitory neurons from the Ascl1+ precursors. In fish, selection of these alternative neurotransmitter fates is controlled by the dynamic expression of Her6 the homolog of [[HES1]]. Expression of this hairy-like bHLH [[transcription factor]], which represses Neurogenin but is required for Ascl1, is progressively lost from the caudal thalamus but maintained in the prethalamus and in the stripe of rostral thalamic cells. In addition, studies on chick and mice have shown that blocking the Shh pathway leads to absence of the rostral thalamus and substantial decrease of the caudal thalamus. The rostral thalamus will give rise to the reticular nucleus mainly whereby the caudal thalamus will form the relay thalamus and will be further subdivided in the [[thalamic nuclei]].<ref name="cell" />

In humans, a common genetic variation in the promoter region of the [[serotonin transporter]] (the SERT-long and -short allele: [[5-HTTLPR]]) has been shown to affect the development of several regions of the thalamus in adults. People who inherit two short [[allele]]s (SERT-ss) have more neurons and a larger volume in the [[Pulvinar nucleus|pulvinar]] and possibly the limbic regions of the thalamus. Enlargement of the thalamus provides an anatomical basis for why people who inherit two SERT-ss alleles are more vulnerable to [[Major depressive disorder|major depression]], [[post-traumatic stress disorder]], and suicide.<ref>{{cite journal |doi=10.1016/j.biopsych.2006.08.047 |title=5HTTLPR Polymorphism and Enlargement of the Pulvinar: Unlocking the Backdoor to the Limbic System |year=2007 |last1=Young |first1=Keith A. |last2=Holcomb |first2=Leigh A. |last3=Bonkale |first3=Willy L. |last4=Hicks |first4=Paul B. |last5=Yazdani |first5=Umar |last6=German |first6=Dwight C. |journal=Biological Psychiatry |volume=61 |issue=6 |pages=813–8 |pmid=17083920|s2cid=2214561}}</ref>