Control of roof plate development and signaling by Lmx1b in the caudal vertebrate CNS

被引：57

作者：

Chizhikov, VV ^{[1
]}

Millen, KJ ^{[1
]}

机构：

[1] Univ Chicago, Dept Human Genet, Cummings Life Sci Ctr 319, Chicago, IL 60637 USA

来源：

JOURNAL OF NEUROSCIENCE | 2004年 / 24卷 / 25期

关键词：

Lmx1b; roof plate; Lmx1a; dreher; Bmp; Wnt; developing spinal cord;

D O I：

10.1523/JNEUROSCI.0758-04.2004

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Numerous studies have identified the roof plate as an important signaling center controlling dorsal interneuron specification and differentiation in the developing spinal cord. Currently, the molecular pathways of roof plate formation and function are poorly understood. We determined that the LIM-homeodomain transcription factor Lmx1b is sufficient to induce functional roof plate in the early chick developing spinal cord. In the chick, Lmx1b acts upstream of Lmx1a in the roof plate developmental program. Once the roof plate forms, we show that Bmp and Wnt signaling are the major components of Lmx1a/b-dependent roof plate dorsal patterning activity. The roof plate function of Lmx1b is not conserved across vertebrates because Lmx1b is not expressed in mouse roof plate progenitors. Instead, mouse caudal CNS roof plate formation relies entirely on Lmx1a. Lmx1b can, however, partially rescue roof plate development in dreher (Lmx1a(-/-)) mice, indicating that Lmx1b has some functional redundancy to Lmx1a. Furthermore, we demonstrate that the roof plate-inducing activity of Lmx1b can be suppressed by Mash1 (Cash1), which is normally expressed in intermediate neural tube in both chick and mouse. Our data identify Lmx1b as a key regulator of spinal cord roof plate induction and function.

引用

页码：5694 / 5703

页数：10

共 37 条

[1]

Adams KA, 2000, DEVELOPMENT, V127, P1857

[2] Mammalian ELAV-like neuronal RNA-binding proteins HuB and HuC promote neuronal development in both the central and the peripheral nervous systems [J].

Akamatsu, W ;

Okano, HJ ;

Osumi, N ;

Inoue, T ;

Nakamura, S ;

Sakakibara, SI ;

Miura, M ;

Matsuo, N ;

Darnell, RB ;

Okano, H .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (17) :9885-9890

[3] A role for BMP heterodimers in roof plate-mediated repulsion of commissural axons [J].

Butler, SJ ;

Dodd, J .

NEURON, 2003, 38 (03) :389-401

[4] Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome [J].

Chen, H ;

Lun, Y ;

Ovchinnikov, D ;

Kokubo, H ;

Oberg, KC ;

Pepicelli, CV ;

Gan, L ;

Lee, B ;

Johnson, RL .

NATURE GENETICS, 1998, 19 (01) :51-55

[5] Control of roof plate formation by Lmx1a in the developing spinal cord [J].

Chizhikov, VV ;

Millen, KJ .

DEVELOPMENT, 2004, 131 (11) :2693-2705

[6] Lmx1b is essential for the development of serotonergic neurons [J].

Ding, YQ ;

Marklund, U ;

Yuan, WL ;

Yin, J ;

Wegman, L ;

Ericson, J ;

Deneris, E ;

Johnson, RL ;

Chen, ZF .

NATURE NEUROSCIENCE, 2003, 6 (09) :933-938

[7] Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome [J].

Dreyer, SD ;

Zhou, G ;

Baldini, A ;

Winterpacht, A ;

Zabel, B ;

Cole, W ;

Johnson, RL ;

Lee, B .

NATURE GENETICS, 1998, 19 (01) :47-50

[8] Pax6 controls progenitor cell identity and neuronal fate in response to graded shh signaling [J].

Ericson, J ;

Rashbass, P ;

Schedl, A ;

BrennerMorton, S ;

Kawakami, A ;

vanHeyningen, V ;

Jessell, TM ;

Briscoe, J .

CELL, 1997, 90 (01) :169-180

[9] Expression of the LIM-homeodomain gene Lmx1a (dreher) during development of the mouse nervous system [J].

Failli, V ;

Bachy, I ;

Rétaux, S .

MECHANISMS OF DEVELOPMENT, 2002, 118 (1-2) :225-228

[10] Inhibitory effects of ventral signals on the development of Brn-3.0-expressing neurons in the dorsal spinal cord [J].

Fedtsova, N ;

Turner, EE .

DEVELOPMENTAL BIOLOGY, 1997, 190 (01) :18-31

← 1 2 3 4 →