Biomedical Frontiers: Winter 1995, Vol.2, No.2
Developing A Nervous System

During early vertebrate development, certain embryonic neural cells secrete proteins that guide the subsequent growth of the nervous system. Some of these proteins are so fundamental that they help determine whether cells in the nervous system should face to the front or rear relative to the vertical axis of the body. Without these proteins, for example, cells would not know whether they should eventually become sensory or motor neurons.

Dr. Thomas Jessell, professor of biochemistry and molecular biophysics and Howard Hughes Medical Institute investigator, recently isolated two nerve factors, dorsalin-1 and hedgehog, implicated in the dorso-ventral orientation of the developing nervous system. Dorsalin-1 is involved in defining the fates of dorsal sensory cells and hedgehog of ventral cells such as motor neurons.

Besides being important in understanding how the nervous system develops, these factors have potential pharmacological application. As such, patents are pending on the proteins and their use.

Dr. Jessell imagines, for example, that hedgehog might be used as part of a cocktail of factors to enrich for specific classes of neurons in fetal tissue that are now being used in neural transplantation. (See Frontiers, Vol. 1, Issue 3, p. 9.) By taking cells from the ventral region of the fetus's developing mesencephalon, he says, dopaminergic cells may be induced and grown more homogeneously in culture and could then be used for implants in Parkinson's disease. Dopaminergic cells comprise a group of motor neurons that are lost in Parkinson's disease. Currently, a heterogeneous mixture of fetal neural cells is given to patients in clinical trials.

Other applications for hedgehog are for motor nerve cell regeneration and for the screening of drugs that either activate or inhibit the growth of motor nerve cells. Dorsalin-1 might be used in assays to screen for agents that promote bone growth, promote wound healing, treat neural tumors, and regenerate nerve cells.