Genomes and Genes
Gene Symbol: Isl2
Description: insulin related protein 2 (islet 2)
Alias: 3110001N10Rik, insulin gene enhancer protein ISL-2, islet 2
- Edlund T, Jessell T. Progression from extrinsic to intrinsic signaling in cell fate specification: a view from the nervous system. Cell. 1999;96:211-24 pubmed
- Herrera E, Brown L, Aruga J, Rachel R, Dolen G, Mikoshiba K, et al. Zic2 patterns binocular vision by specifying the uncrossed retinal projection. Cell. 2003;114:545-57 pubmed..These data provide evidence for transcriptional coding of axon pathfinding at the midline. ..
- Pfaff S, Mendelsohn M, Stewart C, Edlund T, Jessell T. Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation. Cell. 1996;84:309-20 pubmed..These results show that ISL1 is required for the generation of motor neurons and suggest that motor neuron generation is required for the subsequent differentiation of certain interneurons. ..
- Thaler J, Koo S, Kania A, Lettieri K, Andrews S, Cox C, et al. A postmitotic role for Isl-class LIM homeodomain proteins in the assignment of visceral spinal motor neuron identity. Neuron. 2004;41:337-50 pubmed..All spinal motor neuron subtypes initially express both Isl1 and Isl2, but Isl2 is rapidly downregulated by visceral motor neurons...
- Muller T, Brohmann H, Pierani A, Heppenstall P, Lewin G, Jessell T, et al. The homeodomain factor lbx1 distinguishes two major programs of neuronal differentiation in the dorsal spinal cord. Neuron. 2002;34:551-62 pubmed..We conclude that Lbx1 distinguishes two major neuronal classes in the dorsal spinal cord and is an important determinant of their distinct differentiation programs. ..
- Hazen V, Andrews M, Umans L, Crenshaw E, Zwijsen A, Butler S. BMP receptor-activated Smads confer diverse functions during the development of the dorsal spinal cord. Dev Biol. 2012;367:216-27 pubmed publisher..Thus the R-Smads, like the I-Smads, have discrete roles mediating BMP-dependent cellular processes during spinal interneuron development...
- Lei Q, Jeong Y, Misra K, Li S, Zelman A, Epstein D, et al. Wnt signaling inhibitors regulate the transcriptional response to morphogenetic Shh-Gli signaling in the neural tube. Dev Cell. 2006;11:325-37 pubmed..These results identify a transcriptional mechanism that integrates graded Shh and Wnt signaling to define progenitor gene expression domains and cell fates in the neural tube. ..
- Sharma K, Sheng H, Lettieri K, Li H, Karavanov A, Potter S, et al. LIM homeodomain factors Lhx3 and Lhx4 assign subtype identities for motor neurons. Cell. 1998;95:817-28 pubmed..Thus, Lhx3 and Lhx4 act in a binary fashion during a brief period in development to specify the trajectory of motor axons from the neural tube. ..
- Reber M, Burrola P, Lemke G. A relative signalling model for the formation of a topographic neural map. Nature. 2004;431:847-53 pubmed..Molecular genetic experiments, exploiting a combinatorial series of EphA receptor knock-in and knockout mice, confirm the salient predictions of the model, and show that it both describes and predicts topographic mapping. ..
- Dessaud E, Salaün D, Gayet O, Chabbert M, Delapeyrière O. Identification of lynx2, a novel member of the ly-6/neurotoxin superfamily, expressed in neuronal subpopulations during mouse development. Mol Cell Neurosci. 2006;31:232-42 pubmed..Comparison of its spatio-temporal expression pattern with that of two other members of this family, lynx1 and ly-6h, shows that these genes are detected both in distinct and overlapping neuron populations. ..
- Bonanomi D, Chivatakarn O, Bai G, Abdesselem H, Lettieri K, Marquardt T, et al. Ret is a multifunctional coreceptor that integrates diffusible- and contact-axon guidance signals. Cell. 2012;148:568-82 pubmed publisher..Our studies uncover a hierarchical GPI-receptor signaling network that is constructed from combinatorial components and integrated through Ret using ligand coincidence detection. ..
- Elshatory Y, Deng M, Xie X, Gan L. Expression of the LIM-homeodomain protein Isl1 in the developing and mature mouse retina. J Comp Neurol. 2007;503:182-97 pubmed..Taken together, Isl1 is expressed during the maturation of and is later maintained in retinal ganglion cells and subtypes of amacrine and bipolar cells where it may function in the maintenance of these cells into adulthood. ..
- Joksimovic M, Anderegg A, Roy A, Campochiaro L, Yun B, Kittappa R, et al. Spatiotemporally separable Shh domains in the midbrain define distinct dopaminergic progenitor pools. Proc Natl Acad Sci U S A. 2009;106:19185-90 pubmed publisher..This refined ontogenetic definition will expand understanding of dopamine neuron biology and selective susceptibility, and will impact stem cell-derived therapies and models for PD. ..
- Triplett J, Phan A, Yamada J, Feldheim D. Alignment of multimodal sensory input in the superior colliculus through a gradient-matching mechanism. J Neurosci. 2012;32:5264-71 pubmed publisher..Together, these data support a model in which somatosensory inputs into the SC map topographically and establish alignment with visual inputs in the SC using a gradient-matching mechanism. ..
- Rachel R, Dolen G, Hayes N, Lu A, Erskine L, Nowakowski R, et al. Spatiotemporal features of early neuronogenesis differ in wild-type and albino mouse retina. J Neurosci. 2002;22:4249-63 pubmed..These results point to spatiotemporal defects in neuronal production in the albino retina, which could perturb expression of genes that specify cell fate, number, and/or projection phenotype...
- Ericson J, Rashbass P, Schedl A, Brenner Morton S, Kawakami A, van Heyningen V, et al. Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell. 1997;90:169-80 pubmed..2. Pax6 establishes distinct ventral progenitor cell populations and controls the identity of motor neurons and ventral interneurons, mediating graded Shh signaling in the ventral spinal cord and hindbrain. ..
- Huber A, Kania A, Tran T, Gu C, De Marco Garcia N, Lieberam I, et al. Distinct roles for secreted semaphorin signaling in spinal motor axon guidance. Neuron. 2005;48:949-64 pubmed..Thus, Sema3A-Npn-1 and Sema3F-Npn-2 signaling control distinct steps of motor axon growth and guidance during the formation of spinal motor connections. ..
- Sharma K, Leonard A, Lettieri K, Pfaff S. Genetic and epigenetic mechanisms contribute to motor neuron pathfinding. Nature. 2000;406:515-9 pubmed..Nevertheless, elevated occupancy of the axial pathway can override their genetic program, causing some axons to project to alternative targets. ..
- Rebsam A, Bhansali P, Mason C. Eye-specific projections of retinogeniculate axons are altered in albino mice. J Neurosci. 2012;32:4821-6 pubmed publisher..These results suggest that the defects in afferent targeting and activity-dependent refinement in the albino dLGN arise from RGC misspecification together with potential perturbations of early activity patterns in the albino retina...
- Matise M, Joyner A. Expression patterns of developmental control genes in normal and Engrailed-1 mutant mouse spinal cord reveal early diversity in developing interneurons. J Neurosci. 1997;17:7805-16 pubmed..Rather, it is suggested that En-1 may function to distinguish a subset of interneurons during the later maturation of the spinal cord. ..
- Masahira N, Takebayashi H, Ono K, Watanabe K, Ding L, Furusho M, et al. Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells. Dev Biol. 2006;293:358-69 pubmed..These findings demonstrate that motoneurons and oligodendrocytes are not the only cell types originating from this domain. ..
- Arber S, Ladle D, Lin J, Frank E, Jessell T. ETS gene Er81 controls the formation of functional connections between group Ia sensory afferents and motor neurons. Cell. 2000;101:485-98 pubmed..ER81 therefore controls a late step in the establishment of functional sensory-motor circuitry in the developing spinal cord. ..
- Haase G, Dessaud E, Garces A, de Bovis B, Birling M, Filippi P, et al. GDNF acts through PEA3 to regulate cell body positioning and muscle innervation of specific motor neuron pools. Neuron. 2002;35:893-905 pubmed..Thus, GDNF acts as a peripheral signal to induce PEA3 expression in specific motor neuron pools thereby regulating both cell body position and muscle innervation. ..
- Thaler J, Harrison K, Sharma K, Lettieri K, Kehrl J, Pfaff S. Active suppression of interneuron programs within developing motor neurons revealed by analysis of homeodomain factor HB9. Neuron. 1999;23:675-87 pubmed..Thus, MNs actively suppress interneuron genetic programs to establish their identity...
- Kim N, Burden S. MuSK controls where motor axons grow and form synapses. Nat Neurosci. 2008;11:19-27 pubmed
- Caubit X, Thoby Brisson M, Voituron N, Filippi P, Bevengut M, Faralli H, et al. Teashirt 3 regulates development of neurons involved in both respiratory rhythm and airflow control. J Neurosci. 2010;30:9465-76 pubmed publisher..Thus, a single gene, Tshz3, controls the development of diverse components of the circuitry required for breathing. ..
- Lu Q, Sun T, Zhu Z, Ma N, Garcia M, Stiles C, et al. Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell. 2002;109:75-86 pubmed..Neither Olig gene is required for astrocytes. These findings, together with fate mapping analysis of Olig-expressing cells, indicate that oligodendrocytes are derived from Olig-specified progenitors that give rise also to neurons. ..
- Gross M, Dottori M, Goulding M. Lbx1 specifies somatosensory association interneurons in the dorsal spinal cord. Neuron. 2002;34:535-49 pubmed..Lbx1, therefore, plays a critical role in the development of sensory pathways in the spinal cord that relay pain and touch. ..
- De Marco Garcia N, Jessell T. Early motor neuron pool identity and muscle nerve trajectory defined by postmitotic restrictions in Nkx6.1 activity. Neuron. 2008;57:217-31 pubmed publisher..Our findings provide genetic evidence that neurons within motor pools possess an early transcriptional identity that controls target muscle specificity. ..
- Kablar B, Rudnicki M. Development in the absence of skeletal muscle results in the sequential ablation of motor neurons from the spinal cord to the brain. Dev Biol. 1999;208:93-109 pubmed..The epaxial and cutaneous component of dorsal ramus failed to form in the absence of the myotome. Therefore, we conclude that nervous development is more intimately coupled to skeletal myogenesis than has previously been understood. ..
- Luria V, Krawchuk D, Jessell T, Laufer E, Kania A. Specification of motor axon trajectory by ephrin-B:EphB signaling: symmetrical control of axonal patterning in the developing limb. Neuron. 2008;60:1039-53 pubmed publisher..The involvement of ephrin:Eph signaling in guiding both sets of motor axons raises the possibility that other signaling systems function primarily to refine or modulate a core Eph signaling program. ..
- Francius C, Clotman F. Dynamic expression of the Onecut transcription factors HNF-6, OC-2 and OC-3 during spinal motor neuron development. Neuroscience. 2010;165:116-29 pubmed publisher..Together, our data unveil a complex and dynamic expression profile of the OC proteins in spinal MN, which suggests that these factors may participate in regulatory networks that control different steps of motor neuron development. ..
- Triplett J, Owens M, Yamada J, Lemke G, Cang J, Stryker M, et al. Retinal input instructs alignment of visual topographic maps. Cell. 2009;139:175-85 pubmed publisher..These data suggest a general model in which convergent maps use coincident activity patterns to achieve alignment. ..
- Rousso D, Pearson C, Gaber Z, Miquelajauregui A, Li S, Portera Cailliau C, et al. Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS. Neuron. 2012;74:314-30 pubmed publisher..Together, these data reveal a Foxp-based transcriptional mechanism that regulates the integrity and cytoarchitecture of neuroepithelial progenitors. ..
- Vrieseling E, Arber S. Target-induced transcriptional control of dendritic patterning and connectivity in motor neurons by the ETS gene Pea3. Cell. 2006;127:1439-52 pubmed..These findings suggest that target-induced transcriptional programs control MN dendrite orientation and play a crucial role in the establishment of sensory-motor connections in the spinal cord. ..
- Yang X, Arber S, William C, Li L, Tanabe Y, Jessell T, et al. Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation. Neuron. 2001;30:399-410 pubmed..Our results demonstrate that AChR expression is patterned in the absence of innervation, raising the possibility that similarly prepatterned muscle-derived cues restrict axon growth and initiate synapse formation. ..
- Briscoe J, Sussel L, Serup P, HARTIGAN O CONNOR D, Jessell T, Rubenstein J, et al. Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature. 1999;398:622-7 pubmed..Thus, Nkx2.2 has an essential role in interpreting graded Shh signals and selecting neuronal identity. ..
- Quina L, Pak W, Lanier J, Banwait P, Gratwick K, Liu Y, et al. Brn3a-expressing retinal ganglion cells project specifically to thalamocortical and collicular visual pathways. J Neurosci. 2005;25:11595-604 pubmed..Brn3a is coexpressed extensively with the closely related factor Brn3b in the embryonic retina, and the effects of the loss of Brn3a in retinal development are not severe, suggesting partial redundancy of function in this gene class. ..
- Lieberam I, Agalliu D, Nagasawa T, Ericson J, Jessell T. A Cxcl12-CXCR4 chemokine signaling pathway defines the initial trajectory of mammalian motor axons. Neuron. 2005;47:667-79 pubmed..In its absence, these neurons adopt a dMN-like trajectory, despite preservation of their vMN transcriptional identity. Thus, the status of Cxcr4 signaling helps to determine the initial axonal trajectory of mammalian motor neurons. ..
- Agalliu D, Takada S, Agalliu I, McMahon A, Jessell T. Motor neurons with axial muscle projections specified by Wnt4/5 signaling. Neuron. 2009;61:708-20 pubmed publisher..Thus, two dorsoventral signaling pathways, mediated by Shh and Wnt4/5, are required to establish an early binary divergence in motor neuron columnar identity. ..
- Helmbacher F, Schneider Maunoury S, Topilko P, Tiret L, Charnay P. Targeting of the EphA4 tyrosine kinase receptor affects dorsal/ventral pathfinding of limb motor axons. Development. 2000;127:3313-24 pubmed..Our data therefore suggest that the level of EphA4 protein in growing limb motor axons is involved in the selection of dorsal versus ventral trajectories, thus contributing to the topographic organisation of motor projections. ..
- Arber S, Han B, Mendelsohn M, Smith M, Jessell T, Sockanathan S. Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron. 1999;23:659-74 pubmed..These findings show that HB9 has an essential function in consolidating the identity of postmitotic MNs. ..
- Sun T, Pringle N, Hardy A, Richardson W, Smith H. Pax6 influences the time and site of origin of glial precursors in the ventral neural tube. Mol Cell Neurosci. 1998;12:228-39 pubmed..that OLPs originate in the ventral-most part of the Pax6-positive VZ, which at earlier times generates somatic (Isl2/Lim3-positive) MNs...
- Grossmann K, Wende H, Paul F, Cheret C, Garratt A, Zurborg S, et al. The tyrosine phosphatase Shp2 (PTPN11) directs Neuregulin-1/ErbB signaling throughout Schwann cell development. Proc Natl Acad Sci U S A. 2009;106:16704-9 pubmed publisher..Together, our genetic and biochemical analyses demonstrate that Shp2 is an essential component in the transduction of Nrg1/ErbB signals. ..
- Andrieu D, Meziane H, Marly F, Angelats C, Fernandez P, Muscatelli F. Sensory defects in Necdin deficient mice result from a loss of sensory neurons correlated within an increase of developmental programmed cell death. BMC Dev Biol. 2006;6:56 pubmed..Finally we also exclude an anti-proliferative role of Necdin in developing sensory neurons. Overall, our data show clearly that, in early development of the nervous system, Necdin is an anti-apoptotic or survival factor. ..
- Erskine L, Williams S, Brose K, Kidd T, Rachel R, Goodman C, et al. Retinal ganglion cell axon guidance in the mouse optic chiasm: expression and function of robos and slits. J Neurosci. 2000;20:4975-82 pubmed
- Williams S, Mann F, Erskine L, Sakurai T, Wei S, Rossi D, et al. Ephrin-B2 and EphB1 mediate retinal axon divergence at the optic chiasm. Neuron. 2003;39:919-35 pubmed..EphB1 null mice exhibit a dramatically reduced ipsilateral projection, suggesting that this receptor contributes to the formation of the ipsilateral retinal projection, most likely through its repulsive interaction with ephrin-B2. ..
- Ozaki S, Snider W. Initial trajectories of sensory axons toward laminar targets in the developing mouse spinal cord. J Comp Neurol. 1997;380:215-29 pubmed..The pathways taken by developing sensory afferents are compatible with the idea that cells in inappropriate laminae exert inhibitory influences on sensory axons which regulate their laminar specificity. ..
- Ashrafi S, Lalancette Hébert M, Friese A, Sigrist M, Arber S, Shneider N, et al. Wnt7A identifies embryonic ?-motor neurons and reveals early postnatal dependence of ?-motor neurons on a muscle spindle-derived signal. J Neurosci. 2012;32:8725-31 pubmed publisher..Furthermore, using Wnt7a expression as an early marker of ?-MN identity, we demonstrate a previously unknown dependence of ?-MNs on a muscle spindle-derived, GDNF-independent signal during the first postnatal week. ..