Signaling in neuronal development
We study how intercellular signals regulate development. We focus on the developing vertebrate spinal cord and limb as model systems.

Innervations of the limb musculature results in the establishment of a topographic map between neurons of spinal cord motor pools and their specific muscle targets. An early event in the formation of this map is a binary decision made by two groups of motor neurons that directs their axons into either dorsal or ventral limb tissue, a process that involves intrinsic neuronal properties and peripheral guidance cues.

The question we are addressing is how axons interpret peripheral information in deciding when to project ventrally. We have chosen to do so by asking how axons that normally innervate ventral limb respond to a peripheral environment that lacks its normal targets. Will they fail to enter dorsal limb territory, consistent with an absolute ventral-only projection decision, or will they enter the only limb tissue they detect, indicating a normally relative preference for ventral over dorsal?

We are also exploring the molecular control of the decision making process by screening candidate regulatory molecules, examining their expression in bidorsal and biventral limb mutants, and asking how motor projection choices are affected in gain and loss of function experiments in mouse and chick.

The construction of functional neural circuits demands that a neuron make precise connections and that it acquire differentiated properties appropriate for its specific function. While it is clear that this process is choreographed by the interplay of intrinsic neuronal properties and extrinsic cues, a key question is what roles specific growth factor signals play in early circuit assembly.

Sympathetic preganglionic neurons are autonomic motor neurons that project from the spinal cord to peripheral postganglionic neurons of the sympathetic ganglia, and provide the major outflow connection between the central and peripheral parts of the sympathetic branch of the autonomic nervous system.We have identified the SPNs, which are located in thoracic segments, as a spinal cord population that uniquely transduces BMP family signals shortly after they become postmitotic.

We are using gain and loss of function experiments in intact embryos and explant cultures to explore the developmental role of this BMP signal, and also to investigate the source of the signal and how the signal and responses to it are regulated.

• Vargesson N., Luria V., Messina I., Erskine L., and Laufer, E. Expression patterns of Robo and Slit family members during vertebrate limb development. Mech Dev. (2001) 106, 175.
• Vargesson, N. and Laufer, E. Smad7 misexpression during embryonic angiogenesis causes vascular dilation and malformations independently of vascular smooth muscle cell function. Dev. Biol. (2001) 240, 499-516.
• Liu J. P., Laufer, E., and Jessell, T.M. Assigning the Positional Identity of Spinal Motor Neurons: Rostrocaudal Patterning of Hox-c Protein Expression by FGFs, Gdf11, and Retinoids. Neuron. (2001) 32, 997-1012.
• Firulli B. A., Krawchuk, D., Centonze V. E., Vargesson N., Virshup D. M., Conway S. J., Cserjesi P.,Laufer E., and Firulli A. B. Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities. Nat. Genet. (2005) 37, 373-381.

IMAGE 2


Click image to enlarge.

IMAGE 3


Click image to enlarge

IMAGE 4


Click image to enlarge.

IMAGE 5


Click image to enlarge.