Beyond Laminar Fate: Toward a Molecular Classification of Cortical Projection/Pyramidal NeuronsHevner R.F.a · Daza R.A.M.a · Rubenstein J.L.R.c · Stunnenberg H.d · Olavarria J.F.b · Englund C.a
aDepartment of Pathology, University of Washington, Harborview Medical Center and bDepartment of Psychology, University of Washington, Seattle, Wash., and cDepartment of Psychiatry, Nina Ireland Laboratories, UCSF, SanFrancisco, Calif., USA; dDepartment of Molecular Biology, University of Nijmegen, Nijmegen, TheNetherlands
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Article / Publication Details
Cortical projection neurons exhibit diverse morphological, physiological, and molecular phenotypes, but it is unknown how many distinct types exist. Many projection cell phenotypes are associated with laminar fate (radial position), but each layer may also contain multiple types of projection cells. We have investigated two hypotheses: (1) that different projection cell types exhibit characteristic molecular expression profiles and (2) that laminar fates are determined primarily by molecular phenotype. We found that several transcription factors were differentially expressed by projection neurons, even within the same layer: Otx1 and Er81, for example, were expressed by different neurons in layer 5. Retrograde tracing showed that Er81 was expressed in corticospinal and corticocortical neurons. In contrast, Otx1 has been detected only in corticobulbar neurons [Weimann et al., Neuron 1999;24:819–831]. Birthdating demonstrated that different molecularly defined types were produced sequentially, in overlapping waves. Cells adopted laminar fates characteristic of their molecular phenotypes, regardless of cell birthday. Molecular markers also revealed the locations of different projection cell types in the malformed cortex of reeler mice. These studies suggest that molecular profiles can be used advantageously for classifying cortical projection cells, for analyzing their neurogenesis and fate specification, and for evaluating cortical malformations.
© 2003 S. Karger AG, Basel
- Alcántara S, Ruiz M, D’Arcangelo G, Ezan F, de Lecea L, Curran T, Sotelo C, Soriano E (1998): Regional and cellular patterns of reelin mRNA expression in the forebrain of the developing and adult mouse. J Neurosci 18:7779–7799.
- Anderson SA, Eisenstat DD, Shi L, Rubenstein JLR (1997): Interneuron migration from basal forebrain to neocortex: Dependence on Dlx genes. Science 278:474–476.
Anderson SA, Kaznowski CE, Horn C, Rubenstein JLR, McConnell SK (2002): Distinct origins of neocortical projection neurons and interneurons in vivo. Cereb Cortex 12:702–709.
Angevine JB, Sidman RL (1961): Autoradiographic study of cell migration during histogenesis of cerebral cortex in the mouse. Nature 192:766–768.
- Arimatsu Y, Ishida M (2002): Distinct neuronal populations specified to form corticocortical and corticothalamic projections from layer VI of developing cerebral cortex. Neuroscience 114:1033–1045.
- Arimatsu Y, Ishida M, Sato M, Kojima M (1999): Corticocortical associative neurons expressing latexin: Specific cortical connectivity formed in vivo and in vitro. Cereb Cortex 9:569–576.
- Bulfone A, Smiga SM, Shimamura K, Peterson A, Puelles L, Rubenstein JLR (1995): T-Brain-1: A homolog of Brachyury whose expression defines molecularly distinct domains within the cerebral cortex. Neuron 15:63–78.
- Caviness VS Jr (1982): Neocortical histogenesis in normal and reeler mice: A developmental study based upon [3H]thymidine autoradiography. Dev Brain Res 4:293–302.
- Caviness VS Jr, Takahashi T, Nowakowski RS (1995): Numbers, time and neocortical neuronogenesis: A general developmental and evolutionary model. Trends Neurosci 18:379–383.
- Caviness VS Jr, Takahashi T, Nowakowski RS (2000): Neocortical malformation as consequence of nonadaptive regulation of neuronogenetic sequence. Ment Retard Dev Disabil Res Rev 6:22–33.
- Chan C-H, Godinho LN, Thomaidou D, Tan S-S, Gulisano M, Parnavelas JG (2001): Emx1 is a marker for pyramidal neurons of the cerebral cortex. Cereb Cortex 11:1191–1198.
Csillik AE, Okuno E, Csillik B, Knyihár E, Vécsei L (2002): Expression of kynurenine aminotransferase in the subplate of the rat and its possible role in the regulation of programmed cell death. Cereb Cortex 12:1193–1201.
- D’Arcangelo G, Miao GG, Chen S-C, Soares HD, Morgan JI, Curran T (1995): A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature 374:719–723.
- Derer P, Derer M (1990): Cajal-Retzius cell ontogenesis and death in mouse brain visualized with horseradish peroxidase and electron microscopy. Neuroscience 36:839–856.
- Frantz GD, Bohner AP, Akers RM, McConnell SK (1994a): Regulation of the POU domain gene SCIP during cerebral cortical development. J Neurosci 14:472–485.
- Frantz GD, Weimann JM, Levin ME, McConnell SK (1994b): Otx1 and Otx2 define layers and regions in developing cerebral cortex and cerebellum. J Neurosci 14:5725–5740.
- Gawlas K, Stunnenberg HG (2000): Differential binding and transcriptional behavior of two highly related orphan receptors, RORα4 and RORβ1. Biochim Biophys Acta 1494:236–241.
- Gonchar Y, Burkhalter A (1997): Three distinct families of GABAergic neurons in rat visual cortex. Cereb Cortex 7:347–358.
Gorski JA, Talley T, Qiu M, Puelles L, Rubenstein JLR, Jones KR (2002): Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. J Neurosci 22:6309–6314.
- Helms AW, Johnson JE (2003): Specification of dorsal spinal cord interneurons. Curr Opin Neurobiol 13:42–49.
- Hendricks T, Francis N, Fyodorov D, Deneris ES (1999): The ETS domain factor Pet-1 is an early and precise marker of central serotonergic neurons and interacts with a conserved element in serotonergic genes. J Neurosci 19:10348–10356.
Hevner RF, Neogi T, Englund C, Daza RAM, Fink A (2003): Cajal-Retzius cells in the mouse: Transcription factors, neurotransmitters, and birthdays suggest a pallial origin. Dev Brain Res, in press.
- Hevner RF, Shi L, Justice N, Hsueh Y-P, Sheng M, Smiga S, Bulfone A, Goffinet AM, Campagnoni AT, Rubenstein JLR (2001): Tbr1 regulates differentiation of the preplate and layer 6. Neuron 29:353–366.
Isshiki T, Pearson B, Holbrook S, Doe CQ (2001): Drosophila neuroblasts sequentially express transcription factors which specify the temporal identity of their neuronal progeny. Cell 106:511–521.
- Ivy GO, Killackey HP (1982): Ontogenetic changes in the projections of neocortical neurons. J Neurosci 2:735–743.
- Jessell TM (2000): Neuronal specification in the spinal cord: Inductive signals and transcriptional codes. Nat Rev Genet 1:20–29.
- Kitamura K, Yanazawa M, Sugiyama N, Miura H, Iizuka-Kogo A, Kusaka M, Omichi K, Suzuki R, Kato-Fukui Y, Kamiirisa K, Matsuo M, Kamijo S, Kasahara M, Yoshioka H, Ogata T, Fukuda T, Kondo I, Kato M, Dobyns WB, Yokoyama M, Morohashi K (2002): Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. Nat Genet 32:359–369.
- Koester SE, O’Leary DDM (1993): Connectional distinction between callosal and subcortically projecting cortical neurons is determined prior to axon extension. Dev Biol 160:1–14.
- Kozloski J, Hamzei-Sichani F, Yuste R (2001): Stereotyped position of local synaptic targets in the neocortex. Science 293:868–872.
- Landry CF, Pribyl TM, Ellison JA, Givogri MI, Kampf K, Campagnoni CW, Campagnoni AT (1998): Embryonic expression of the myelin basic protein gene: Identification of a promoter region that targets transgene expression to pioneer neurons. J Neurosci 18:7315–7327.
- Lavdas AA, Grigoriou M, Pachnis V, Parnavelas JG (1999): The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex. J Neurosci 19:7881–7888.
- Lewis JW, Olavarria JF (1995): Two rules for callosal connectivity in striate cortex of the rat. J Comp Neurol 361:119–137.
Li C-P, Olavarria JF, Greger BE (1995): Occipital cortico-pyramidal projection in hypothyroid rats. Dev Brain Res 89:227–234.
- Livesey FJ, Cepko CL (2001): Vertebrate neural cell-fate determination: Lessons from the retina. Nat Rev Neurosci 2:109–118.
- McEvilly RJ, Ortiz de Diaz M, Schonemann MD, Hooshmand F, Rosenfeld MG (2002): Transcriptional regulation of cortical neuron migration by POU domain factors. Science 295:1528–1532.
- Meyer G, Goffinet AM (1998): Prenatal development of reelin-immunoreactive neurons in the human neocortex. J Comp Neurol 397:29–40.
- Olavarria JF, Van Sluyters RC (1995): Comparison of the patterns of callosal connections in lateral parietal cortex of the rat, mouse and hamster. Anat Embryol 191:239–242.
- O’Leary DDM, Bicknese A, De Carlos JA, Heffner CD, Koester SE, Kutka LJ, Terashima T (1990): Target selection by cortical axons: Alternative mechanisms to establish axonal connections in the developing brain. Cold Spring Harb Symp Quant Biol 55:453–468.
- Pesold C, Impagnatiello F, Pisu MG, Uzunov DP, Costa E, Guidotti A, Caruncho HJ (1998): Reelin is preferentially expressed in neurons synthesizing γ-aminobutyric acid in cortex and hippocampus of adult rats. Proc Natl Acad Sci USA 95:3221–3226.
- Polleux F, Dehay C, Kennedy H (1998): Neurogenesis and commitment of corticospinal neurons in reeler. J Neurosci 18:9910–9923.
- Price DJ, Aslam S, Tasker L, Gillies K (1997): Fates of the earliest generated cells in the developing murine neocortex. J Comp Neurol 377:414–422.
- Rakic P (1974): Neurons in rhesus monkey visual cortex: Systematic relation between time of origin and eventual disposition. Science 183:425–427.
- Shirasaki R, Pfaff SL (2002): Transcriptional codes and the control of neuronal identity. Annu Rev Neurosci 25:251–281.
Stühmer T, Anderson SA, Ekker M, Rubenstein JLR (2002): Ectopic expression of the Dlx genes induces glutamic acid decarboxylase and Dlx expression. Development 129:245–252.
- Sugitani Y, Nakai S, Minowa O, Nishi M, Jishage K, Kawano H, Mori K, Ogawa M, Noda T (2002): Brn-1 and Brn-2 share crucial roles in the production and positioning of mouse neocortical neurons. Genes Dev 16:1760–1765.
- Takahashi T, Goto T, Miyama S, Nowakowski RS, Caviness VS Jr (1999): Sequence of neuron origin and neocortical laminar fate: Relation to cell cycle of origin in the developing murine cerebral wall. J Neurosci 19:10357–10371.
Thomson AM, Bannister AP (2003): Interlaminar connections in the neocortex. Cereb Cortex 13:5–14.
- Vetter ML, Brown NL (2001): The role of basic helix-loop-helix genes in vertebrate retinogenesis. Semin Cell Dev Biol 12:491–498.
- Wang Z, McCormick DA (1993): Control of firing mode of corticotectal and corticopontine layer V burst-generating neurons by norepinephrine, acetylcholine, and 1S,3R-ACPD. J Neurosci 13:2199–2216.
- Weimann JM, Zhang YA, Levin ME, Devine WP, Brület P, McConnell SK (1999): Cortical neurons require Otx1 for the refinement of exuberant axonal projections to subcortical targets. Neuron 24:819–831.
- Xu B, Zang K, Ruff NL, Zhang YA, McConnell SK, Stryker MP, Reichardt LF (2000): Cortical degeneration in the absence of neurotrophin signaling: Dendritic retraction and neuronal loss after removal of the receptor TrkB. Neuron 26:233–245.
- Zhou C, Qiu Y, Pereira FA, Crair MC, Tsai SY, Tsai M-J (1999): The nuclear orphan receptor COUP-TFI is required for differentiation of subplate neurons and guidance of thalamocortical axons. Neuron 24:847–859.
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