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An all-round talent: the protein Nulp1 is involved in many developmental
processes in men and mice
Martina Saar
The development of single cells to a functional organ and finally a complete organism is an
amazing interplay of numerous factors. Since their identification, a class of proteins called
basic helix-loop-helix (bHLH) proteins has been found to be involved in various
developmental processes. Generally, proteins are classified according to certain patterns or
motifs in their basic components, the amino acids, or structures that are formed due to specific
interactions between the amino acids. Characteristically, the bHLH proteins feature a stretch
of basic amino acids (which can be charged positively) and two sections that are organized as
helices and are connected by a flexible loop region. In the HLH region, one of the helices is
typically smaller than the other and allows either two identical proteins to connect to form a
homodimer, or two different proteins to build a heterodimer. The basic region is found in
most but not all HLH proteins and specifically binds to variations of certain DNA sequences.
Many bHLH protein dimers work as activators of transcription (the first step in decoding
DNA to make proteins). Nuclear localized protein-1 (Nulp1) is a recently identified protein
found in organs such as heart, kidney and brain during mouse embryonic development. It
contains an HLH domain as well as a stretch of basic residues that closely resembles the
transcriptional activation domain of some bHLH proteins. Nulp1 has been found in the cell
nucleus, indicating its probable involvement in transcriptional processes. The human form
hNulp1 also contains a bHLH domain and has been found to be particularly abundant in adult
heart. Nulp1 is also expressed in tumor cells, in mouse and human alike. Interestingly, a
smaller variant of the Nulp1 protein was found in tumors in addition to the protein in regular
cells, suggesting a tumor specific variant that may be linked to cell malignancy.
The aim of this project was to investigate more closely the expression of Nulp1 in mouse
brain and other organs and to analyze the truncated form that is found in tumor cells. This was
done via a visualization of the protein with a fluorescent color in tissue sections. Furthermore,
the amount of protein in several areas of the brain as well as liver, kidney and muscle was
quantified. The intended analysis of the tumor variant could not be performed successfully
due to methodical problems. Nevertheless, I confirmed that Nulp1 is expressed at notably
higher levels in embryonic mouse brain, liver, kidney, lung and several other organs. In very
young mice and also adults I measured a particularly high expression in brain and especially
within the cerebellum, the part of the brain mainly responsible for orientation and movement.
In the other above mentioned adult organs Nulp1 could not be identified indisputably. The
fluorescence pictures that were taken further revealed that the area within the cerebellum
where the highest expression was observed shifted postnatally. While the outermost cell
layers showed the strongest signals for Nulp1 in very young mice, in adult mice the most
intense signals were seen within an inner layer. This finding suggests a role of Nulp1 in the
maturation of cerebellar neurons that takes place postnatally and involves the inner-directed
migration of developing cells. In addition to these developmental functions that Nulp1 seems
to have, thre future will show if there is a further involvement in programmed cell death
and/or cell malignancy.
Degree project in Biology, winter 2006
Examensarbete i biologi, 10p, winter 2006
Department of Biology Education and
Department of Cell Neurosciences, Neurobiology, Uppsala University
Supervisor: Prof. Dan Lindholm and PhD student Hakan Steen